2-Phenyl substituted imidazotriazinones as phosphodiesterase inhibitors

ABSTRACT

The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.

The present invention relates to 2-phenyl-substituted imidazotriazinones, to processes for their preparation and to their use as pharmaceuticals, in particular as inhibitors of cGMP-metabolizing phosphodiesterases.

The published specification DE 28 11 780 describes imidazotriazines as bronchodilators having spasmolytic activity and inhibitory activity against phosphodiesterases which metabolize cyclic adenosin monophosphate (cAMP-PDEs, nomenclature according to Beavo: PDE-III and PDE-IV). An inhibitory action against phosphodiesterases which metabolize cyclic guanosin monophosphate (cGMP-PDEs, nomenclature according to Beavo and Reifsnyder (Trends in Pharmacol. Sci. 11, 150-155, 1990) PDE-I, PDE-II and PDE-V) has not been described. Compounds having a sulphonamide group in the aryl radical in the 2-position are not claimed. Furthermore, FR 22 13 058, CH 59 46 71, DE 22 55 172, DE 23 64 076 and EP 000 9384 describe imidazotriazinones which do not have a substituted aryl radical in the 2-position and are likewise said to be bronchodilators having cAMP-PDE inhibitory action.

WO 94/28902 describes pyrazolopyriridinones which are suitable for treating impotence.

The compounds according to the invention are potent inhibitors either of one or of more of the phosphodiesterases which metabolize cyclic guanosin 3′,5_49 -monophosphate (cGMP-PDEs). According to the nomenclature of Beavo and Reifsnyder (Trends in Pharmacol. Sci. 11, 150-155, 1990) these are the phosphodiesterase isoenzymes PDE-I, PDE-II and PDE-V.

An increase of the cGMP concentration can lead to beneficial antiaggregatory, antithrombotic, antiprolific, antivasospastic, vasodilative, natriuretic and diuretic effects. It can influence the short- or long-term modulation of vascular and cardiac inotropy, of the pulse and of cardiac conduction (J. C. Stoclet, T. Keravis, N. Komas and C. Kugnier, Exp. Opin. Invest. Drugs (1995), 4 (11), 1081-1100).

The present invention, accordingly, provides 2-phenyl-substituted imidazotriazinones of the general formula (I)

-   -   in which     -   R¹ represents hydrogen or straight-chain or branched alkyl         having up to 4 carbon atoms,     -   R² represents straight-chain alkyl having up to 4 carbon atoms,     -   R³ and R⁴ are identical or different and each represents         hydrogen or represents straight-chain or branched alkenyl or         alkoxy having in each case up to 8 carbon atoms, or represents a         straight-chain or branched alkyl chain having up to 10 carbon         atoms which is optionally interrupted by an oxygen atom and         which is optionally mono- or polysubstituted by identical or         different substituents selected from the group consisting of         trifluoromethyl, trifluoromethoxy, hydroxyl, halogen, carboxyl,         benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl         having up to 6 carbon atoms and/or by radicals of the formulae         —SO₃H, -(A)_(a)-NR⁷R⁸, —O—CO—NR^(7′)R^(8′), —S(O)_(b)—R⁹,         —P(O)(OR¹⁰)(OR¹¹),     -   in which     -   a and b are identical or different and each represents a number         0 or 1,     -   A represents a radical CO or SO₂,     -   R⁷, R^(7′), R⁸ and R^(8′) are identical or different and each         represents hydrogen, or represents cycloalkyl having 3 to 8         carbon atoms, aryl having 6 to 10 carbon atoms, a 5- to         6-membered unsaturated, partially unsaturated or saturated,         optionally benzo-fused heterocycle having up to 3 heteroatoms         from the group consisting of S, N and O, where the         abovementioned ring systems are optionally mono- or         polysubstituted by identical or different substituents selected         from the group consisting of hydroxyl, nitro, trifluoromethyl,         trifluoromethoxy, carboxyl, halogen, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 6 carbon         atoms or by a group of the formula —(SO₂)_(c)—NR¹²R¹³,     -   in which     -   c represents a number 0 or 1,     -   R¹² and R¹³ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 5         carbon atoms,     -   or     -   R⁷, R^(7′), R⁸ and R^(8′) each represent straight-chain or         branched alkoxy having up to 6 carbon atoms, or represents         straight-chain or branched alkyl having up to 8 carbon atoms         which is optionally mono- or polysubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, halogen, aryl having 6 to 10 carbon atoms,         straight-chain or branched alkoxy or alkoxycarbonyl having in         each case up to 6 carbon atoms or by a group of the formula         —(CO)_(d)—NR¹⁴R¹⁵,     -   in which     -   R¹⁴ and R¹⁵ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms,     -   and     -   d represents a number 0 or 1,     -   or     -   R⁷ and R⁸ and/or R^(7′) and R^(8′) together with the nitrogen         atom form a 5- to 7-membered saturated heterocycle which may         optionally contain a further heteroatom from the group         consisting of S and O or a radical of the formula —NR¹⁶,     -   in which     -   R¹⁶ represents hydrogen, aryl having 6 to 10 carbon atoms,         benzyl, a 5- to 7-membered aromatic or saturated heterocycle         having up to 3 heteroatoms from the group consisting of S, N and         O which is optionally substituted by methyl, or represents         straight-chain or branched alkyl having up to 6 carbon atoms         which is optionally substituted by hydroxyl,     -   R⁹ represents aryl having 6 to 10 carbon atoms, or represents         straight-chain or branched alkyl having up to 4 carbon atoms,     -   R¹⁰ and R¹¹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms, and/or the alkyl chain listed above under R³/R⁴ is         optionally substituted by cycloalkyl having 3 to 8 carbon atoms,         aryl having 6 to 10 carbon atoms or by a 5- to 7-membered         partially unsaturated, saturated or unsaturated, optionally         benzo-fused heterocycle which may contain up to 4 heteroatoms         from the group consisting of S, N and O or a radical of the         formula —NR¹⁷,     -   in which     -   R¹⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl,         straight-chain or branched acyl or alkoxy having in each case up         to 4 carbon atoms, or represents straight-chain or branched         alkyl having up to 6 carbon atoms which is optionally mono- or         polysubstituted by identical or different substituents selected         from the group consisting of hydroxyl and straight-chain or         branched alkoxy having up to 6 carbon atoms,     -   and where aryl and the heterocycle are optionally mono- or         polysubstituted by identical or different substituents selected         from the group consisting of nitro, halogen, -SO₃H,         straight-chain or branched alkyl or alkoxy having in each case         up to 6 carbon atoms, hydroxyl, trifluoromethyl,         trifluoromethoxy and/or by a radical of the formula         —SO₂—NR¹⁸R¹⁹,     -   in which     -   R¹⁸ and R¹¹⁹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 6         carbon atoms,     -   and/or     -   R³ or R⁴ represents a group of the formula —NR²⁰R²¹,     -   in which     -   R²⁰ and R²¹ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   and/or     -   R³ or R⁴ represents adamantyl, or represents radicals of the         formulae     -   or represents cycloalkyl having 3 to 8 carbon atoms, aryl having         6 to 10 carbon atoms or represents a 5- to 7-membered partially         unsaturated, saturated or unsaturated, optionally benzo-fused         heterocycle which may contain up to 4 heteroatoms from the group         consisting of S, N and O, or a radical of the formula —NR²²,     -   in which     -   R²² has the meaning of R¹⁶ given above and is identical to or         different from it, or represents carboxyl, formyl or         straight-chain or branched acyl having up to 5 carbon atoms,     -   and where cycloalkyl, aryl and/or the heterocycle are optionally         mono- or polysubstituted by identical or different substituents         selected from the group consisting of halogen, triazolyl,         trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or         branched acyl or alkoxycarbonyl having in each case up to 6         carbon atoms, nitro and/or by groups of the formulae —SO₃H,         —OR²³, (SO₂)_(e)NR²⁴R²⁵, —P(O)(OR²⁶)(OR²⁷),     -   in which     -   e represents a number 0 or 1,     -   R²³ represents a radical of the formula     -   represents cycloalkyl having 3 to 7 carbon atoms, or represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms which is optionally substituted by cycloalkyl         having 3 to 7 carbon atoms, benzyloxy, tetrahydropyranyl,         tetrahydrofuranyl, straight-chain or branched alkoxy or         alkoxycarbonyl having in each case up to 6 carbon atoms,         carboxyl, benzyloxycarbonyl or phenyl which for its part may be         mono- or polysubstituted by identical or different substituents         selected from the group consisting of straight-chain or branched         alkoxy having up to 4 carbon atoms, hydroxyl and halogen,     -   and/or alkyl which is optionally substituted by radicals of the         formulae —CO—NR²⁸R²⁹ or —CO—R³⁰,     -   in which     -   R²⁸ and R²⁹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 8         carbon atoms, or     -   R²⁸ and R²⁹ together with the nitrogen atom form a 5- to         7-membered saturated heterocycle which may optionally contain a         further heteroatom from the group consisting of S and O,     -   and     -   R³⁰ represents phenyl or adamantyl,     -   R²⁴ and R²⁵ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   R²⁶ and R²⁷ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them

1and/or cycloalkyl, aryl and/or the heterocycle are optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, carboxyl, by a 5- to 7-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, or by groups of the formula —SO₂—R³¹, P(O)(OR³²)(OR³³) or —NR³⁴R³⁵,

-   -   in which     -   R³¹ represents hydrogen or has the meaning of R⁹ given above and         is identical to or different from it,     -   R³² and R³³ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them,     -   R³⁴ and R³⁵ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 6         carbon atoms which is optionally substituted by hydroxyl or by         straight-chain or branched alkoxy having up to 4 carbon atoms,         or     -   R³⁴ and R³⁵ together with the nitrogen atom form a 5- to         6-membered saturated heterocycle which may contain a further         heteroatom from the group consisting of S and 0, or a radical of         the formula —NR³⁶,     -   in which     -   R³⁶ represents hydrogen, hydroxyl, straight-chain or branched         alkoxycarbonyl having up to 7 carbon atoms or straight-chain or         branched alkyl having up to 5 carbon atoms which is optionally         substituted by hydroxyl,     -   or     -   R³ and R⁴ together with the nitrogen atom form a 5- to         7-membered unsaturated or saturated or partially unsaturated,         optionally benzo-fused heterocycle which may optionally contain         up to 3 heteroatoms from the group consisting of S, N and O, or         a radical of the formula —NR³⁷,     -   in which     -   R³⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl,         straight-chain or branched acyl, alkoxy or alkoxycarbonyl having         in each case up to 4 carbon atoms, or represents straight-chain         or branched alkyl having up to 6 carbon atoms which is         optionally mono- or polysubstituted by identical or different         substituents selected from the group consisting of hydroxyl,         trifluoromethyl, carboxyl, straight-chain or branched alkoxy or         alkoxycarbonyl having in each case up to 6 carbon atoms, or by         groups of the formula -(D)_(f)-NR³⁸R³⁹, —CO—(CH₂)_(g)—O—CO—R⁴⁰,         —CO—(CH₂)_(h)—OR⁴¹ or —P(O)(OR⁴²)(OR⁴³),     -   in which     -   g and h are identical or different and each represents a number         1, 2, 3 or 4,     -   and     -   f represents a number 0 or 1,     -   D represents a group of the formula —CO or —SO₂,     -   R³⁸ and R³⁹ are identical or different and each has the meaning         of R⁷ and R⁸ given above,     -   R⁴⁰ represents straight-chain or branched alkyl having up to 6         carbon atoms,     -   R⁴¹ represents straight-chain or branched alkyl having up to 6         carbon atoms,     -   R⁴² and R⁴³ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms,     -   or     -   R³⁷ represents a radical of the formula —(CO)_(i)-E,     -   in which     -   i represents a number 0 or 1,     -   E represents cycloalkyl having 3 to 7 carbon atoms or benzyl,         represents aryl having 6 to 10 carbon atoms or a 5- to         6-membered aromatic heterocycle having up to 4 heteroatoms from         the group consisting of S, N and O, where the abovementioned         ring systems are optionally mono- or polysubstituted by         identical or different constituents selected from the group         consisting of nitro, halogen, —SO₃H, straight-chain or branched         alkoxy having up to 6 carbon atoms, hydroxyl, trifluoromethyl,         trifluoromethoxy, or by a radical of the formula —SO₂—NR⁴R⁴⁵,     -   in which     -   R⁴⁴ and R⁴⁵ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   or     -   E represents radicals of the formulae     -   and the heterocycle listed under R³ and R⁴, which is formed         together with the nitrogen atom, is optionally mono- or         polysubstituted, if appropriate also geminally, by identical or         different substituents selected from the group consisting of         hydroxyl, formyl, carboxyl, straight-chain or branched acyl or         alkoxycarbonyl having in each case up to 6 carbon atoms, nitro         and groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷),     -   in which     -   R⁴⁶ and R⁴⁷ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them,     -   R⁴⁸ represents hydroxyl or straight-chain or branched alkoxy         having up to 4 carbon atoms,     -   represents a number 0 or 1,     -   and     -   R⁴⁹ and R⁵⁰ are identical or different and have the meanings of         R¹⁴ and R¹⁵ given above,     -   and/or the heterocycle listed under R³ and R⁴, which is formed         together with the nitrogen atom, is optionally substituted by         straight-chain or branched alkyl having up to 6 carbon atoms         which is optionally mono- or polysubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, halogen, carboxyl, cycloalkyl or cycloalkyloxy having         in each case 3 to 8 carbon atoms, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 6 carbon         atoms, or by a radical of the formula —SO₃H, —NR⁵¹R⁵² or         P(O)OR⁵³OR⁵⁴,     -   in which     -   R⁵¹ and R⁵² are identical or different and each represents         hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched         alkyl or alkoxy having in each case up to 6 carbon atoms,     -   R⁵³ and R⁵⁴ are identical or different and have the meanings of         R¹⁰ and R¹¹ given above,     -   and/or the alkyl is optionally substituted by aryl having 6 to         10 carbon atoms which for its part may be mono- or         polysubstituted by identical or different substituents selected         from the group consisting of halogen, hydroxyl, straight-chain         or branched alkoxy having up to 6 carbon atoms, or by a group of         the formula —NR^(51′)R^(52′),     -   in which     -   R^(51′) and R^(52′) have the meanings of R⁵¹ and R⁵² given above         and are identical to or different from them,     -   and/or the heterocycle listed under R³ and R⁴, which is formed         together with the nitrogen atom, is optionally substituted by         aryl having 6 to 10 carbon atoms or by a 5- to 7-membered         saturated, partially unsaturated or unsaturated heterocycle         having up to 3 heteroatoms from the group consisting of S, N and         O, optionally also attached via a nitrogen function, where the         ring systems for their part may be substituted by hydroxyl or by         straight-chain or branched alkyl or alkoxy having in each case         up to 6 carbon atoms,     -   or     -   R³ and R⁴ together with the nitrogen atom form radicals of the         formulae     -   R⁵ and R⁶ are identical or different and each represents         hydrogen, straight-chain or branched alkyl having up to 6 carbon         atoms, hydroxyl or represents straight-chain or branched alkoxy         having up to 6 carbon atoms,     -   and their salts, hydrates, N-oxides and isomeric forms.

The compounds according to the invention may exist in stereoisomeric forms which are related either as image and mirror image (enantiomers), or which are not related as image and mirror image (diastereomers). The invention relates both to the enantiomers or diastereomers and to their respective mixtures. The racemic forms can, just like the diastereomers, be separated in a known manner into the stereoisomerically pure constituents.

The substances according to the invention may also be present as salts. In the context of the invention, preference is given to physiologically acceptable salts.

Physiologically acceptable salts can be salts of the compounds according to the invention with inorganic or organic acids. Preference is given to salts with inorganic acids, such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or to salts with organic carboxylic or sulphonic acids, such as, for example, acetic acid, maleic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulphonic acid, ethanesulphonic acid, phenylsulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid.

Physiologically acceptable salts can also be metal or ammonium salts of the compounds according to the invention. Particular preference is given to, for example, sodium, potassium, magnesium or calcium salts, and also to ammonium salts which are derived from ammonia or organic amines, such as, for example, ethylamine, di- or triethylamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol, arginine, lysine, ethylenediamine or 2-phenylethylamine.

In the context of the invention, an optionally benzo-fused heterocycle generally represents a saturated, partially unsaturated or unsaturated 5- to 7-membered heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N and O. Examples which may be mentioned are: azepine, diazepine, indolyl, isoquinolyl, quinolyl, benzo[b]thiophene, benzo[b]furanyl, pyridyl, thienyl, tetrahydrofuranyl, tetrahydropyranyl, furyl, pyrrolyl, thiazolyl, triazolyl, tetrazolyl, isoxazolyl, imidazolyl, morpholinyl, thiomorpholinyl, pyrrolidinyl, piperazinyl, N-methylpiperazinyl or piperidinyl. Preference is given to quinolyl, furyl, pyridyl, thienyl, piperidinyl, pyrrolidinyl, piperazinyl, azepine, diazepine, thiazolyl, triazolyl, tetrazolyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl and thiomorpholinyl.

In the context of the invention, a straight-chain or branched acyl radical having 1 to 6 carbon atoms represents, for example acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, butylcarbonyl, isobutylcarbonyl, pentylcarbonyl and hexylcarbonyl. Preference is given to a straight-chain or branched acyl radical having 1 to 4 carbon atoms. Particular preference is given to acetyl and ethylcarbonyl.

In the context of the invention, a straight-chain or branched alkoxy radical having 1 to 6 or 1 to 4 carbon atoms represents methoxy, ethoxy, n-propoxy, isopropoxy, tert-butoxy, n-pentoxy and n-hexoxy. Preference is given to a straight-chain or branched alkoxy radical having 1 to 6, 1 to 4 or 1 to 3 carbon atoms. Particular preference is given to a straight-chain or branched alkoxy radical having 1 to 3 carbon atoms.

In the context of the invention, a straight-chain or branched alkoxycarbonyl radical having 1 to 6 carbon atoms represents, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and tert-butoxycarbonyl. Preference is given to a straight-chain or branched alkoxycarbonyl radical having 1 to 4 carbon atoms. Particular preference is given to a straight-chain or branched alkoxycarbonyl radical having 1 to 3 carbon atoms.

In the context of the invention, a straight-chain or branched alkyl radical having 1 to 4, 1 to 6, 1 to 8 and 1-10 carbon atoms represents, for example, methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl. Preference is given to straight-chain or branched alkyl radicals having 1 to 3, 1 to 4 or 1 to 8 carbon atoms. Particular preference is given to straight-chain or branched alkyl radicals having 1 to 4 or 1 to 3 carbon atoms.

In the context of the invention, straight-chain alkyl having up to 4 carbon atoms represents, for example, methyl, ethyl, n-propyl and n-butyl.

(C₆C₁₀)-Aryl generally represents an aromatic radical having 6 to 10 carbon atoms. Preferred aryl radicals are phenyl and naphthyl.

In the context of the invention, cycloalkyl having 3 to 8 or 3 to 7 carbon atoms represents, for example, cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl, cycloheptyl or cyclooctyl. Preference is given to: cyclopropyl, cyclopentyl and cyclohexyl.

In the context of the invention, cycloalkyloxy having 3 to 8 carbon atoms represents cyclopropyloxy, cyclopentyloxy, cyclobutyloxy, cyclohexyloxy, cycloheptyloxy or cyclooctyloxy. Preference is given to: cyclopropyloxy, cyclopentyloxy and cyclohexyloxy.

In the context of the invention, halogen generally represents fluorine, chlorine, bromine and iodine. Preference is given to fluorine, chlorine and bromine. Particular preference is given to fluorine and chlorine.

In the context of the invention and depending on the abovementioned substituents, a 5- to 6-membered or 7-membered saturated heterocycle, which may contain a further heteroatom from the group consisting of S, N and O represents, for example, morpholinyl, piperidinyl, piperazinyl, tetrahydropyranyl or tetrahydrofuranyl. Preference is given to morpholinyl, tetrahydropyranyl, piperidinyl and piperazinyl.

In the context of the invention, a 5- to 6-membered aromatic heterocycle having up to 3 or 4 heteroatoms from the group consisting of S, O and N represents, for example, pyridyl, pyrimidyl, pyridazinyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl or imidazolyl. Preference is given to pyridyl, pyrimidyl, pyridazinyl, furyl and thiazolyl.

In the context of the invention, a 5- to 6-membered unsaturated, partially unsaturated and saturated heterocycle which may contain up to 3 or 4 heteroatoms from the group consisting of S, O and N represents, for example, pyridyl, pyrimidyl, pyridazinyl, thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, piperidinyl, piperazinyl or morpholinyl. Preference is given to pyridyl, pyrimidyl, piperazinyl, pyridazinyl, morpholinyl, furyl and thiazolyl.

The compounds according to the invention, in particular the salts, may also be present as hydrates. In the context of the invention, hydrates are those compounds which contain water in the crystal. Such compounds may contain one or more, typically 1 to 5, equivalents of water. Hydrates can be prepared, for example, by crystallizing the compound in question from water or from a water-containing solvent.

Preference is given to compounds of the general formula (I) according to the invention

-   -   in which     -   R¹ represents straight-chain or branched alkyl having up to 3         carbon atoms,     -   R² represents straight-chain alkyl having up to 3 carbon atoms,     -   R³ and R⁴ are identical or different and each represents         hydrogen or represents straight-chain or branched alkenyl or         alkoxy having in each case up to 6 carbon atoms, or represents a         straight-chain or branched alkyl chain having up to 8 carbon         atoms which is optionally interrupted by an oxygen atom and         which is optionally mono- to trisubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, fluorine, chlorine, carboxyl, benzyloxycarbonyl,         straight-chain or branched alkoxycarbonyl having up to 5 carbon         atoms, and/or by radicals of the formulae —SO₃H, -(A)_(a)-NR⁷R⁸,         —O—CO—NR^(7′)R^(8′), —S(O)_(b)—R⁹, —P(O)(OR¹⁰)(OR¹¹),     -   in which     -   a and b are identical or different and each represents a number         0 or 1,     -   A represents a radical CO or SO₂,     -   R⁷, R^(7′), R⁸ and R^(8′) are identical or different and each         represents hydrogen, or cyclopropyl, cyclopentyl, cyclohexyl,         cycloheptyl, phenyl, piperidinyl and pyridyl, where the         abovementioned ring systems are optionally mono- to         trisubstituted by identical or different substituents selected         from the group consisting of hydroxyl, nitro, trifluoromethyl,         trifluoromethoxy, carboxyl, fluorine, chlorine, straight-chain         or branched alkoxy or alkoxycarbonyl having in each case up to 4         carbon atoms, or by a group of the formula —(SO₂)_(c)—NR¹²R¹³,     -   in which     -   c represents a number 0 or 1,     -   R¹² and R¹³ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms,     -   or     -   R⁷, R^(7′), R⁸ and R^(8′) each represent straight-chain or         branched alkoxy having up to 3 carbon atoms, or represents         straight-chain or branched alkyl having up to 7 carbon atoms         which is optionally mono- or polysubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 4 carbon         atoms, or by a group of the formula —(CO)_(d)—NR¹⁴R¹⁵,     -   in which     -   R¹⁴ and R¹⁵ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 3         carbon atoms,     -   and     -   d represents a number 0 or 1,     -   or     -   R⁷ and R⁸ and/or R^(7′) and R^(8′) together with the nitrogen         atom form a pyrrolidinyl, morpholinyl, piperidinyl or triazolyl         ring or radicals of the formulae     -   in which     -   R¹⁶ represents hydrogen, phenyl, benzyl, morpholinyl,         pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl,         or represents straight-chain or branched alkyl having up to 5         carbon atoms which is optionally substituted by hydroxyl,     -   R⁹ represents straight-chain or branched alkyl having up to 3         carbon atoms,     -   R¹⁰ and R¹¹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 3         carbon atoms,     -   and/or the alkyl chain listed under R³/R⁴ is optionally         substituted by cyclopropyl, cyclopentyl, cyclohexyl,         cycloheptyl, phenyl, pyridyl, quinolyl, pyrrolidinyl, pyrimidyl,         morpholinyl, furyl, piperidinyl, tetrahydrofuranyl or by         radicals of the formulae     -   in which     -   R¹⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl,         straight-chain or branched acyl or alkoxy having in each case up         to 3 carbon atoms, or represents straight-chain or branched         alkyl having up to 4 carbon atoms which is optionally mono- to         trisubstituted by identical or different substituents selected         from the group consisting of hydroxyl and straight-chain or         branched alkoxy having up to 4 carbon atoms,     -   and where phenyl and the heterocycles are optionally mono- to         trisubstituted by identical or different substituents selected         from the group consisting of nitro, fluorine, chlorine, —SO₃H,         straight-chain or branched alkyl or alkoxy having in each case         up to 4 carbon atoms, hydroxyl, and/or by a radical of the         formula —SO₂ NR¹⁸R¹⁹,     -   in which     -   R¹⁸ and R¹⁹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms,     -   and/or     -   R³ or R⁴ represents a group of the formula —NR²⁰R²¹,     -   in which     -   R²⁰ and R²¹ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   and/or     -   R³ or R⁴ represents adamantyl, or represents radicals of the         formulae     -   or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl,         morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl,         tetrahydrofuranyl, tetrahydropyranyl or represents radicals of         the formulae     -   in which     -   R²² has the meaning of R¹⁶ given above and is identical to or         different from it, or represents carboxyl, formyl or         straight-chain or branched acyl having up to 3 carbon atoms,     -   and where cycloalkyl, phenyl and/or the heterocycles are         optionally mono- to trisubstituted by identical or different         substituents selected from the group consisting of fluorine,         chlorine, triazolyl, trifluoromethyl, trifluoromethoxy,         carboxyl, straight-chain or branched acyl or alkoxycarbonyl         having in each case up to 5 carbon atoms, nitro and/or by groups         of the formulae —SO₃H, —OR²³, (SO₂)_(e)NR²⁴R²⁵,         —P(O)(OR²⁶)(OR²⁷),     -   in which     -   e represents a number 0 or 1,     -   R²³ represents a radical of the formula     -   represents cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl or         cycloheptyl,     -   represents hydrogen or straight-chain or branched alkyl having         up to 4 carbon atoms which may optionally be substituted by         cyclopropyl, cyclopentyl, cyclohexyl, benzyloxy,         tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 4 carbon         atoms, benzyloxycarbonyl or phenyl which for its part may be         mono- or polysubstituted by identical or different substituents         selected from the group consisting of straight-chain or branched         alkoxy having up to 3 carbon atoms, hydroxyl, fluorine and         chlorine,     -   and/or where alkyl is optionally substituted by radicals of the         formulae —CO—NR²⁸R²⁹ or —CO—R³⁰,     -   in which     -   R²⁸ and R²⁹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 5         carbon atoms, or     -   R²⁸ and R²⁹ together with the nitrogen atom form a morpholinyl,         pyrrolidinyl or piperidinyl ring,     -   and     -   R³⁰ represents phenyl or adamantyl,     -   R²⁴ and R²⁵ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   R²⁶ and R²⁷ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them     -   and/or cycloalkyl, phenyl and/or the heterocycles are optionally         substituted by straight-chain or branched alkyl having up to 4         carbon atoms which is optionally substituted by hydroxyl,         carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl,         tetrahydrofuranyl, triazolyl or by groups of the formula         —SO₂—R³¹, —P(O)(OR³²)(OR³³) or —NR³⁴R³⁵,     -   in which     -   R³¹ has the meaning of R⁹ given above and is identical to or         different from it,     -   R³² and R³³ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them,     -   R³⁴ and R³⁵ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 5         carbon atoms which is optionally substituted by hydroxyl or         straight-chain or branched alkoxy having up to 3 carbon atoms,         or     -   R³⁴ and R³⁵ together with the nitrogen atom form a morpholinyl,         triazolyl or thiomorpholinyl ring or a radical of the formula     -   in which     -   R³⁶ represents hydrogen, hydroxyl, straight-chain or branched         alkoxycarbonyl having up to 5 carbon atoms or straight-chain or         branched alkyl having up to 4 carbon atoms which is optionally         substituted by hydroxyl,     -   or     -   R³ and R⁴ together with the nitrogen atom form a morpholinyl,         thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of         the formula     -   in which     -   R³⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl,         straight-chain or branched acyl, alkoxy or alkoxycarbonyl having         in each case up to 4 carbon atoms, or represents straight-chain         or branched alkyl having up to 5 carbon atoms which is         optionally mono- to trisubstituted by identical or different         substituents selected from the group consisting of hydroxyl,         trifluoromethyl, carboxyl, straight-chain or branched alkoxy or         alkoxycarbonyl having in each case up to 4 carbon atoms, or by         groups of the formula -(D)_(f)-NR³⁸R³⁹, —CO—(CH₂)_(g)—O—CO—R⁴⁰,         —CO—(CH₂)_(h)—OR⁴¹ or —P(O)(OR⁴²)(OR⁴³),     -   in which     -   g and h are identical or different and each represents a number         1, 2 or 3,     -   and     -   f represents a number 0 or 1,     -   D represents a group of the formula —CO or —SO₂,     -   R³⁸ and R³⁹ are identical or different and have the meanings of         R⁷ and R⁸ given above,     -   R⁴⁰ represents straight-chain or branched alkyl having up to 4         carbon atoms,     -   R⁴¹ represents straight-chain or branched alkyl having up to 4         carbon atoms,     -   R⁴² and R⁴³ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 3         carbon atoms,     -   or     -   R³⁷ represents a radical of the formula —(CO)_(i)-E,     -   in which     -   i represents a number 0 or 1,     -   E represents cyclopentyl, cyclohexyl, cycloheptyl, benzyl,         phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned         ring systems are optionally mono- or disubstituted by identical         or different substituents selected from the group consisting of         nitro, fluorine, chlorine, —SO₃H, straight-chain or branched         alkoxy having up to 4 carbon atoms, hydroxyl, trifluoromethyl,         trifluoromethoxy or by a radical of the formula —SO₂—NR⁴⁴R⁴⁵,     -   in which     -   R⁴⁴ and R⁴⁵ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   or     -   E represents radicals of the formulae     -   and the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally mono- to         trisubstituted, optionally also geminally, by identical or         different substituents selected from the group consisting of         hydroxyl, formyl, carboxyl, straight-chain or branched acyl or         alkoxycarbonyl having in each case up to 5 carbon atoms, nitro         and groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷),     -   in which     -   R⁴⁶ and R 47 have the meanings of R¹⁰ and R¹¹ given above and         are identical to or different from them,     -   R⁴⁸ represents hydroxyl or straight-chain or branched alkoxy         having up to 3 carbon atoms,     -   j represents a number 0 or 1,     -   and     -   R⁴⁹ and R⁵⁰ are identical or different and have the meanings of         R¹⁴ and R¹⁵ given above,     -   and/or the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally substituted by         straight-chain or branched alkyl having up to 5 carbon atoms         which is optionally mono- or polysubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl,         cyclopentyl, cyclohexyl, cycloheptyl, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 4 carbon         atoms, or by a radical of the formula —SO₃H, —NR⁵¹R⁵² or         —P(O)OR⁵³OR⁴,     -   in which     -   R⁵¹ and R⁵² are identical or different and each represents         hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched         alkyl or alkoxy having in each case up to 4 carbon atoms,     -   R⁵³ and R⁵⁴ are identical or different and have the meanings of         R¹⁰ and R¹¹ given above,     -   and/or the alkyl is optionally substituted by phenyl which for         its part may be mono- to trisubstituted by identical or         different substituents selected from the group consisting of         fluorine, chlorine, hydroxyl, straight-chain or branched alkoxy         having up to 4 carbon atoms, or by a group of the formula         —NR^(51′)R^(52′),     -   in which     -   R^(51′) and R^(52′) have the meanings of R⁵¹ and R⁵² given above         and are identical to or different from them,     -   and/or the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally substituted by         phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl,         optionally also attached via a nitrogen function, where the ring         systems for their part may be substituted by hydroxyl or by         straight-chain or branched alkyl or alkoxy having in each case         up to 5 carbon atoms,     -   or     -   R³ and R⁴ together with the nitrogen atom form radicals of the         formulae     -   R⁵ and R⁶ are identical or different and each represents         hydrogen, hydroxyl or represents straight-chain or branched         alkoxy having up to 4 carbon atoms,     -   and their salts, N-oxides, hydrates and isomeric forms.

Particular preference is given to compounds of the general formula (I) according to the invention

-   -   in which     -   R¹ represents straight-chain or branched alkyl having up to 3         carbon atoms,     -   R² represents straight-chain alkyl having up to 3 carbon atoms,     -   R³ and R⁴ are identical or different and each represents         hydrogen or represents straight-chain or branched alkenyl or         alkoxy having in each case up to 4 carbon atoms, or represents a         straight-chain or branched alkyl chain having up to 6 carbon         atoms which is optionally interrupted by an oxygen atom and         which is optionally mono- to trisubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, fluorine, chlorine, carboxyl, straight-chain or         branched alkoxycarbonyl having up to 4 carbon atoms, and/or by         radicals of the formulae —SO₃H, —(A)_(a)-NR⁷R⁸,         —O—CO—NR^(7′)R^(8′), —S(O)_(b)—R⁹, —P(O)(OR¹⁰)(OR¹¹),     -   in which     -   a and b are identical or different and each represents a number         0 or 1,     -   A represents a radical CO or SO₂,     -   R⁷, R^(7′), R⁸ and R^(8′) are identical or different and each         represents hydrogen, or represents cyclopentyl, cyclohexyl,         cycloheptyl, phenyl, piperidinyl and pyridyl, where the         abovementioned ring systems are optionally mono- or         disubstituted by identical or different substituents selected         from the group consisting of hydroxyl, nitro, carboxyl,         fluorine, chlorine, straight-chain or branched alkoxy or         alkoxycarbonyl having in each case up to 3 carbon atoms, or by a         group of the formula —(SO₂)_(c)—NR¹²R¹³,     -   in which     -   c represents a number 0 or 1,     -   R¹² and R¹³ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 3         carbon atoms,     -   or     -   R⁷, R^(7′), R⁸ and R^(8′) each represent methoxy, or represent         straight-chain or branched alkyl having up to 6 carbon atoms         which is optionally mono- or disubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 3 carbon         atoms, or by a group of the formula —(CO)_(d)—NR¹⁴R¹⁵,     -   in which     -   R¹⁴ and R¹⁵ are identical or different and each represents         hydrogen, methyl or ethyl,     -   and     -   d represents a number 0 or 1,     -   or     -   R⁷ and R⁸ and/or R^(7′) and R^(8′) together with the nitrogen         atom form a morpholinyl, piperidinyl or triazolyl ring or         radicals of the formulae     -   in which     -   R¹⁶ represents hydrogen, phenyl, benzyl, morpholinyl,         pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl,         or represents straight-chain or branched alkyl having up to 3         carbon atoms which is optionally substituted by hydroxyl,     -   R⁹ represents methyl,     -   R¹⁰ and R¹¹ are identical or different and each represents         hydrogen, methyl or ethyl,     -   and/or the alkyl chain listed under R^(3/)R⁴ is optionally         substituted by cyclopropyl, cyclopentyl, cyclohexyl,         cycloheptyl, morpholinyl, furyl, tetrahydrofuranyl, or by         radicals of the formulae     -   in which     -   R¹⁷ represents hydrogen, hydroxyl, formyl, acetyl or alkoxy         having up to 3 carbon atoms, or represents straight-chain or         branched alkyl having up to 3 carbon atoms which is optionally         mono- or disubstituted by identical or different substituents         selected from the group consisting of hydroxyl and         straight-chain or branched alkoxy having up to 3 carbon atoms,     -   and where phenyl and the heterocycles are optionally mono- to         trisubstituted by identical or different substituents selected         from the group consisting of fluorine, chlorine, —SO₃H,         straight-chain or branched alkyl or alkoxy having in each case         up to 3 carbon atoms, hydroxyl, and/or by a radical of the         formula —SO₂—NR¹⁸R¹⁹,     -   in which     -   R¹⁸ and R¹⁹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 3         carbon atoms,     -   and/or     -   R³ or R⁴ represents a group of the formula —NR²⁰R²¹,     -   in which     -   R²⁰ and R²¹ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   and/or     -   R³ or R⁴ represents adamantyl, or represents radicals of the         formulae     -   or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl,         morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl,         tetrahydrofuranyl, tetrahydropyranyl, or represents radicals of         the formulae     -   in which     -   R²² has the meaning of R¹⁶ given above and is identical to or         different from it, or represents formyl or acetyl,     -   and where cycloalkyl, phenyl and/or the heterocycles are         optionally mono- or disubstituted by identical or different         substituents selected from the group consisting of fluorine,         chlorine, triazolyl, carboxyl, straight-chain or branched acyl         or alkoxycarbonyl having in each case up to 4 carbon atoms,         nitro, and/or by groups of the formulae —SO₃H, —OR²³,         (SO₂)_(e)NR²⁴R²⁵, —P(O)(OR²⁶)(OR²⁷),     -   in which     -   e represents a number 0 or 1,     -   R²³ represents a radical of the formula     -   represents cyclopropyl, cyclopentyl, cyclobutyl or cyclohexyl,         represents hydrogen or straight-chain or branched alkyl having         up to 3 carbon atoms which is optionally substituted by         cyclopropyl, cyclohexyl, benzyloxy, tetrahydropyranyl,         straight-chain or branched alkoxy or alkoxycarbonyl having in         each case up to 3 carbon atoms, benzyloxycarbonyl or phenyl         which for its part may be mono- or disubstituted by identical or         different substituents selected from the group consisting of         methoxy, hydroxyl, fluorine or chlorine,     -   and/or where alkyl is optionally substituted by radicals of the         formulae —CO—NR²⁸R²⁹ or —CO—R³⁰,     -   in which     -   R²⁸ and R²⁹ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 4         carbon atoms, or     -   R²⁸ and R²⁹ together with the nitrogen atom form a morpholinyl,         pyrrolidinyl or piperidinyl ring,     -   and     -   R³⁰ represents phenyl or adamantyl,     -   R²⁴ and R²⁵ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   R²⁶ and R²⁷ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them     -   and/or cycloalkyl, phenyl and/or the heterocycles are optionally         substituted by straight-chain or branched alkyl having up to 3         carbon atoms which is optionally substituted by hydroxyl,         carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl,         tetrahydrofuranyl, triazolyl or by groups of the formula         —SO₂—R³¹, P(O)(OR³²)(OR³³) or —NR³⁴R³⁵,     -   in which     -   R³¹ represents methyl,     -   R³² and R³³ have the meanings of R¹⁰ and R¹¹ given above and are         identical to or different from them,     -   R³⁴ and R³⁵ are identical or different and each represents         hydrogen or straight-chain or branched alkyl having up to 3         carbon atoms which is optionally substituted by hydroxyl or         methoxy, or     -   R³⁴ and R³⁵ together with the nitrogen atom form a morpholinyl,         triazolyl or thiomorpholinyl ring, or a radical of the formula     -   in which     -   R³⁶ represents hydrogen, hydroxyl, straight-chain or branched         alkoxycarbonyl having up to 3 carbon atoms or straight-chain or         branched alkyl having up to 3 carbon atoms which is optionally         substituted by hydroxyl,     -   or     -   R³ and R⁴ together with the nitrogen atom form a morpholinyl,         thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of         the formula     -   in which     -   R³⁷ represents hydrogen, hydroxyl, formyl, straight-chain or         branched acyl, alkoxy or alkoxycarbonyl having in each case up         to 3 carbon atoms, or represents straight-chain or branched         alkyl having up to 4 carbon atoms which is optionally mono- or         disubstituted by identical or different substituents selected         from the group consisting of hydroxyl, straight-chain or         branched alkoxy or alkoxycarbonyl having in each case up to 3         carbon atoms, or by groups of the formula -(D)_(f-)NR³⁸R³⁹,         —CO—(CH₂)_(g)—O—CO—R⁴⁰, —CO—(CH₂)_(h)—OR⁴¹ or —P(O)(OR⁴²)(OR⁴³),     -   in which     -   g and h are identical or different and each represents a number         1 or 2,     -   and     -   f represents a number 0 or 1,     -   D represents a group of the formula —CO or —SO₂,     -   R³⁸ and R³⁹ are identical or different and have the meanings of         R⁷ and R⁸ given above,     -   R⁴⁰ represents straight-chain or branched alkyl having up to 3         carbon atoms,     -   R⁴¹ represents straight-chain or branched alkyl having up to 3         carbon atoms,     -   R⁴² and R⁴³ are identical or different and each represents         hydrogen, methyl or ethyl,     -   or     -   R³⁷ represents a radical of the formula —(CO)_(i)-E,     -   in which     -   i represents a number 0 or 1,     -   E represents cyclopentyl, benzyl, phenyl, pyridyl, pyrimidyl or         furyl, where the abovementioned ring systems are optionally         mono- or disubstituted by identical or different substituents         selected from the group consisting of nitro, fluorine, chlorine,         —SO₃H, straight-chain or branched alkoxy having up to 3 carbon         atoms, hydroxyl, or by a radical of the formula —SO₂—NR⁴⁴R⁴⁵,     -   in which     -   R⁴⁴ and R⁴⁵ have the meanings of R¹⁸ and R¹⁹ given above and are         identical to or different from them,     -   or     -   E represents radicals of the formulae     -   and the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally mono- to         trisubstituted, optionally also geminally, by identical or         different substituents selected from the group consisting of         hydroxyl, formyl, carboxyl, straight-chain or branched acyl or         alkoxycarbonyl having in each case up to 3 carbon atoms, or         groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷),     -   in which     -   R⁴⁶ and R 47 have the meanings of R¹⁰ and R¹¹ given above and         are identical to or different from them,     -   R⁴⁸ represents hydroxyl or methoxy,     -   j represents a number 0 or 1,     -   and     -   R⁴⁹ and R⁵⁰ are identical or different and have the meanings of         R¹⁴ and R¹⁵ given above,     -   and/or the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally substituted by         straight-chain or branched alkyl having up to 4 carbon atoms         which is optionally mono- to trisubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl,         cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl         having in each case up to 3 carbon atoms, or by a radical of the         formula —SO₃H, —NR⁵¹R⁵² or P(O)OR⁵³OR⁵⁴,     -   in which     -   R⁵¹ and R⁵² are identical or different and each represents         hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched         alkyl or alkoxy having in each case up to 3 carbon atoms,     -   R⁵³ and R⁵⁴ are identical or different and have the meanings of         R¹⁰ and R¹¹ given above,     -   and/or the alkyl is optionally substituted by phenyl which for         its part may be mono- to disubstituted by identical or different         substituents selected from the group consisting of fluorine,         chlorine, hydroxyl, methoxy, or by a group of the formula         —NR^(51′)R^(52′),     -   in which     -   R^(51′) and R^(52′) have the meanings of R⁵¹ and R⁵² given above         and are identical to or different from them,     -   and/or the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally substituted by         phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, if         appropriate also attached via a nitrogen function, where the         ring systems for their part may be substituted by hydroxyl or by         straight-chain or branched alkyl or alkoxy having in each case         up to 3 carbon atoms,     -   or     -   R³ and R⁴ together with the nitrogen atom form radicals of the         formulae     -   R⁵ and R⁶ are identical or different and each represents         hydrogen, hydroxyl or represents straight-chain or branched         alkoxy having up to 3 carbon atoms,     -   and their salts, N-oxides, hydrates and isomeric forms.

Very particular preference is given to compounds of the general formula (I),

-   -   in which     -   R¹ represents methyl or ethyl,     -   R² represents ethyl or propyl,     -   R³ and R⁴ are identical or different and each represents a         straight-chain or branched alkyl chain having up to 5 carbon         atoms which is optionally substituted up to two times by         identical or different substituents selected from the group         consisting of hydroxyl and methoxy,     -   or     -   R³ and R⁴ together with the nitrogen atom form a piperidinyl,         morpholinyl, thiomorpholinyl ring, or a radical of the formula     -   in which     -   R³⁷ represents hydrogen, formyl, straight-chain or branched acyl         or alkoxycarbonyl having in each case up to 3 carbon atoms, or         represents straight-chain or branched alkyl having up to 3         carbon atoms which is optionally mono- or disubstituted by         identical or different substituents selected from the group         consisting of hydroxyl, carboxyl, straight-chain or branched         alkoxy or alkoxycarbonyl having in each case up to 3 carbon         atoms, or by groups of the formulae -(D)_(f)-NR³⁸R³⁹ or         —P(O)(OR⁴²)(OR⁴³),     -   in which     -   f represents a number 0 or 1,     -   D represents a group of the formula —CO,     -   R³⁸ and R³⁹ are identical or different and each represents         hydrogen or methyl,     -   R⁴² and R⁴³ are identical or different and each represents         hydrogen, methyl or ethyl,     -   or     -   R³⁷ represents cyclopentyl,     -   and the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally mono- or         disubstituted, optionally also geminally, by identical or         different substituents selected from the group consisting of         hydroxyl, formyl, carboxyl, straight-chain or branched acyl or         alkoxycarbonyl having in each case up to 3 carbon atoms, or         groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷) or —(CO)_(i)NR⁴⁹R⁵⁰,     -   in which     -   R⁴⁶ and R⁴⁷ are identical or different and each represents         hydrogen, methyl or ethyl,     -   j represents a number 0 or 1,     -   and     -   R⁴⁹ and R⁵⁰ are identical or different and each represents         hydrogen or methyl     -   and/or the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally substituted by         straight-chain or branched alkyl having up to 3 carbon atoms         which is optionally mono- or disubstituted by identical or         different substituents selected from the group consisting of         hydroxyl, carboxyl, or by a radical of the formula P(O)OR⁵³OR⁵⁴,     -   in which     -   R⁵³ and R⁵⁴ are identical or different and each represents         hydrogen, methyl or ethyl,     -   and/or the heterocycles listed under R³ and R⁴, which are formed         together with the nitrogen atom, are optionally substituted by         pyrrolidinyl or piperidinyl attached via nitrogen,     -   R⁵ represents hydrogen,     -   and     -   R⁶ represents ethoxy or propoxy,     -   and their salts, hydrates, N-oxides and isomeric forms.

Likewise, very particular preference is given to those compounds of the general formula (I) according to the invention in which R⁵ represents hydrogen and the radicals R⁶ and —SO₂NR³R⁴ are in a position para to one another at the phenyl ring.

Particularly preferred compounds are listed in Table A. TABLE A Structure

The invention furthermore provides a process for preparing the compounds of the general formula (I) according to the invention, characterized in that

-   -   initially compounds of the general formula (II)     -   in which     -   R¹ and R² are each as defined above     -   and     -   L represents straight-chain or branched alkyl having up to 4         carbon atoms,     -   are converted with compounds of the general formula (III)     -   in which     -   R⁵ and R⁶ are each as defined above,     -   in a two-step reaction in the systems ethanol and phosphorus         oxytrichloride/dichloroethane into the compounds of the general         formula (IV)     -   in which     -   R¹, R², R⁵ and R⁶ are each as defined above,     -   which are reacted in a further step with chlorosulphonic acid to         give the compounds of the general formula (V)     -   in which     -   R¹, R^(2,) R⁵ and R⁶ are each as defined above,     -   which are finally reacted with amines of the general formula         (VI)         HN³R⁴   (VI)     -   in which     -   R³ and R⁴ are each as defined above,     -   in inert solvents.

The process according to the invention can be illustrated using the following scheme as an example:

Solvents which are suitable for the individual steps are the customary organic solvents which do not change under the reaction conditions. These preferably include ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or hydrocarbons, such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, or halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, dichloroethane, trichloroethylene or chlorobenzene, or ethyl acetate, dimethylformamide, hexamethylphosphoric triamide, acetonitrile, acetone, dimethoxyethane or pyridine. It is also possible to use mixtures of the abovementioned solvents. Particular preference is given to ethanol for the first step and dichloroethane for the second step.

The reaction temperature can generally be varied within a relatively wide range. In general, the reaction is carried out in a range of from -20° C. to 200° C., preferably of from 0° C. to 70° C.

The process steps according to the invention are generally carried out under atmospheric pressure. However, it is also possible to operate under superatmospheric pressure or under reduced pressure (for example, in a range of from 0.5 to 5 bar).

The reaction to give the compounds of the general formula (V) is carried out in a temperature range of from 0° C. to room temperature, and at atmospheric pressure.

The reaction with the amines of the general formula (VI) is carried out in one of the abovementioned chlorinated halogens, preferably in dichloromethane.

The reaction temperature can generally be varied within a relatively wide range. In general, the reaction is carried out at temperatures in a range of from −20° C. to 200° C., preferably of from 0° C. to room temperature.

The reaction is generally carried out at atmospheric pressure. However, it is also possible to operate under superatmospheric pressure or under reduced pressure (for example in a range of from 0.5 to 5 bar).

Some of the compounds of the general formula (II) are known, or they are novel, and they can then be prepared by

-   -   converting compounds of the general formula (VII)         R²—CO-T   (VII)     -   in which     -   R² is as defined above     -   and     -   T represents halogen, preferably chlorine,     -   initially by reaction with compounds of the general formula         (VIII)     -   in which     -   R¹ is as defined above     -   in inert solvents, if appropriate in the presence of a base and         trimethylsilyl chloride, into the compounds of the general         formula (IX)     -   in which     -   R¹ and R² are each as defined above,     -   and finally reacting with the compound of the formula (X)     -   in which L is as defined above,     -   in inert solvents, if appropriate in the presence of a base.

Suitable solvents for the individual steps of the process are the customary organic solvents which do not change under the reaction conditions. These preferably include ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether, or hydrocarbons, such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, or halogenated hydrocarbons, such as dichloromethane, trichloromethane, carbon tetrachloride, dichloroethylene, trichloroethylene or chlorobenzene, or ethyl acetate, dimethylformamide, hexamethylphosphoric triamide, acetonitrile, acetone, dimethoxyethane or pyridine. It is also possible to use mixtures of the abovementioned solvents. Particular preference is given to dichloromethane for the first step and to a mixture of tetrahydrofuran and pyridine for the second step.

Suitable bases are generally alkali metal hydrides or alkali metal alkoxides, such as, for example, sodium hydride or potassium tert-butoxide, or cyclic amines, such as, for example, piperidine, pyridine, dimethylaminopyridine or C₁-C₄ alkylamines, such as, for example, triethylamine. Preference is given to triethylamine, pyridine and/or dimethylaminopyridine.

The base is generally employed in an amount of from 1 mol to 4 mol, preferably from 1.2 mol to 3 mol, in each case based on 1 mol of the compound of the formula (X).

The reaction temperature can generally be varied within a relatively wide range. In general, the reaction is carried out in a range of from −20° C. to 200° C., preferably of from 0° C. to 100° C.

The compounds of the general formulae (VII), (VIII), (IX) and (X) are known per se, or they can be prepared by customary methods.

The compounds of the general formula (III) can be prepared by

-   -   reacting compounds of the general formula (XI)     -   in which     -   R⁵ and R⁶ are each as defined above     -   with ammonium chloride in toluene and in the presence of         trimethylaluminium in hexane in a temperature range of from         −20° C. to room temperature, preferably at 0° C. and atmospheric         pressure, and reacting the resulting amidine, if appropriate in         situ, with hydrazine hydrate.

The compounds of the general formula (XI) are known per se, or they can be prepared by customary methods.

Some of the compounds of the general formula (IV) are known, or they are novel, in which case they can be prepared by known methods [cf. David R. Marshall, Chemistry and Industry, 2 May 1983, 331-335].

Compounds of the general formula (V) are novel per se, however, they can be prepared from the compounds of the general formula (IV) in accordance with the publication Organikum, VEB Deutscher Verlag der Wissenschaften, Berlin 1974, pages 338-339.

The compounds of the general formula (I) according to the invention have an unforeseeable useful pharmacological activity spectrum.

They inhibit either one or more of the cGMP-metabolizing phosphodiesterases (PDE I, PDE II and PDE V). This results in an increase of cGMP. The differentiated expression of the phosphodiesterases in different cells, tissues and organs, as well as the differentiated subcellular localization of these enzymes, in combination with the selective inhibitors according to the invention make it possible to selectively address the various cGMP-regulated processes.

Moreover, the compounds according to the invention enhance the activity of substances such as, for example EDRF (endothelium derived relaxing factor), ANP (atrial natriuretic peptide), of nitrovasodilators and all other substances which increase the cGMP concentration in a manner different from that of phosphodiesterase inhibitors.

They can therefore be employed in pharmaceuticals for treating cardiovascular disorders, such as, for example, for treating hypertension, neuronal hypertonia, stable and unstable angina, peripheral and cardial vascularpathies, arrhythmiae, for treating thromboembolic disorders and ischaemias such as myocardial infarction, stroke, transistory and ischaemic attacks, angina pectoris, obstruction of peripheral circulation, prevention of restenoses after thrombolysis therapy, percutaneous transluminal angioplasty (PTA), percutaneous transluminal coronary angioplasties (PTCA) and bypass. Furthermore, they may also be of significance for cerebrovascular disorders. Owing to their relaxing action on smooth muscles, they are suitable for treating disorders of the urogenital system such as hypertrophy of the prostate, incontinence and in particular for treating erectile dysfunction and female sexual dysfunction.

Activity of the phosphodiesterases (PDEs)

The cGMP-stimulated PDE II, the cGMP-inhibited PDE III and the cAMP-specific PDE IV were isolated either from porcine or bovine heart myocardium. The Ca²⁺-calmodulin-stimulated PDE I was isolated from porcine aorta, porcine brain or, preferably, from bovine aorta. The cGMP-specific PDE V was obtained from porcine small intestine, porcine aorta, human platelets and, preferably, from bovine aorta. Purification was carried out by anion exchange chromatography over MonoQ® Pharmacia, essentially following the method of M. Hoey and Miles D. Houslay, Biochemical Pharmacology, Vol. 40, 193-202 (1990) and C. Lugman et al., Biochemical Pharmacology, Vol. 35, 1743-1751 (1986).

The enzyme activity is determined using a test mixture of 100 ml in 20 mM tris/HCl-buffer pH 7.5 containing 5 mM MgCl₂, 0.1 mg/ml of bovine serum albumin and either 800 Bq[³H]cAMP or [³H]cGMP. The final concentration of the nucleotides in question is 10⁻⁶ mol/l. The reaction is initiated by addition of the enzyme and the amount of enzyme is such that during the incubation time of 30 min, approximately 50% of the substrate are converted. To test the cGMP-stimulated PDE II, [³H]cAMP is used as substrate and 10⁻⁶ mol/l of non-labelled cGMP are added to the mixture. To test the Ca²⁺-calmodulin-dependent PDE I, 1 mM of CaCl₂ and 0.1 mM of calmodulin are added to the reaction mixture. The reaction is quenched by addition of 100 ml of acetonitrile containing 1 mM cAMP and 1 mM AMP. 100 ml of the reaction mixture are separated by HPLC, and the cleavage products are determined quantitatively on-line using a continuous scintillation counter. The substance concentration measured is the concentration at which the reaction rate is reduced by 50%. Additionally, the “phosphodiesterase [³H] cAMP-SPA enzyme assay” and the “phosphodiesterase [³H] cGMP-SPA enzyme assay” from Amersham Life Science were used for testing. The test was carried out according to the test protocol of the manufacturer. To determine the activity of PDE II, the [³H]cAMP SPA assay was used, and 10⁻⁶ M cGMP were added to the reaction mixture to activate the enzyme. To measure PDE I, 10⁻⁷ M calmodulin and 1 mM CaCl₂ were added to the reaction mixture. PDE V was measured using the [³H]cGMP SPA assay.

Inhibition of the phosphodiesterases in vitro PDE I PDE II PDE V Ex. No. IC₅₀ [nM] IC₅₀ [nM] IC₅₀ [nM] 16 300 >1000 2 19 200 >1000 2 20 200 >1000 2 26 100 >1000 1 27 200 >1000 3 32 100 >1000 4 260  300 >1000 10  275   50 >1000 3 338  200 >1000 5

In principle, inhibition of one or more phosphodiesterases of this type results in an increase of the cGMP concentration. Thus, the compounds are of interest for all therapies in which an increase of the cGMP concentration is considered to be beneficial.

The cardiovascular effects were investigated using SH-rats and dogs. The substances were administered intravenously or orally.

The erection-stimulating action was investigated using rabbits which were awake [Naganuma H, Egashira T, Fuji J, Clinical and Experimental Pharmacology and Physiology 20, 177-183 (1993)]. The substances were administered intravenously, orally or parenterally.

The novel active compounds and their physiologically acceptable salts (for example hydrochlorides, maleates or lactates) can be converted in a known manner into the customary formulations, such as tablets, coated tablets, pills, granules, aerosols, syrups, emulsions, suspensions and solutions, using inert non-toxic, pharmaceutically suitable excipients or solvents. In this case the therapeutically active compound should in each case be present in a concentration from approximately 0.5 to 90% by weight of the total mixture, i.e. in amounts which are sufficient in order to achieve the dosage range indicated.

The formulations are prepared, for example, by extending the active compounds using solvents and/or excipients, if appropriate using emulsifiers and/or dispersants, it optionally being possible, for example, to use organic solvents as auxiliary solvents if the diluent used is water.

Administration is carried out in a customary manner, preferably orally, transdermally or parenterally, for example perlingually, buccally, intravenously, nasally, rectally or inhalatively.

For human use, in the case of oral administration, it is good practice to administer doses of from 0.001 to 50 mg/kg, preferably of 0.01 mg/kg-20 mg/kg. In the case of parenteral administration, such as, for example, via mucous membranes nasally, buccally or inhalatively, it is good practice to use doses of 0.001 mg/kg-0.5 mg/kg.

In spite of this, if appropriate it may be necessary to depart from the amounts mentioned, namely depending on the body weight or the type of administration route, on the individual response towards the medicament, the manner of its formulation and the time or interval at which administration takes place. Thus, in some cases it may be adequate to manage with less than the abovementioned minimum amounts, while in other cases the upper limit mentioned has to be exceeded. In the case of the administration of relatively large amounts, it may be advisable to divide these into several individual doses over the course of the day.

The compounds according to the invention are also suitable for use in veterinary medicine. For use in veterinary medicine, the compounds or their non-toxic salts can be administered in a suitable formulation in accordance with general veterinary practice. Depending on the kind of animal to be treated, the veterinary surgeon can determine the nature of use and the dosage.

Starting Materials

EXAMPLE 1A 2-Butyrylaminopropionic acid

22.27 g (250 mmol) of D,L-alanine and 55.66 g (550 mmol) of triethylamine are dissolved in 250 ml of dichloromethane, and the solution is cooled to 0° C. 59.75 g (550 mmol) of trimethylsilyl chloride are added dropwise, and the solution is stirred for 1 hour at room temperature and for 1 hour at 40° C. After cooling to −10° C., 26.64 g (250 mmol) of butyryl chloride are added dropwise, and the resulting mixture is stirred for 2 hours at −10° C. and for one hour at room temperature.

With ice-cooling, 125 ml of water are added dropwise and the reaction mixture is stirred at room temperature for 15 minutes. The aqueous phase is evaporated to dryness, the residue is titrated with acetone and the mother liquor is filtered off with suction. The solvent is removed and the residue is chromatographed. The resulting product is dissolved in 3N aqueous sodium hydroxide solution and the resulting solution is evaporated to dryness. The residue is taken up in conc. HCl and once more evaporated to dryness. The residue is stirred with acetone, precipitated solid is filtered off with suction and the solvent is removed under reduced pressure. This gives 28.2 g (71%) of a viscous oil which crystallizes after some time.

200 MHz ¹H-NMR (DMSO-d6): 0.84, t, 3H; 1.22, d, 3H; 1.50, hex, 2H; 2.07, t, 2H; 4.20, quin., 1H; 8.09, d, 1H.

EXAMPLE 2A 2-Butyrylamino butyric acid

25.78 g of 2-aminobutyric acid (250 mmol) and 55.66 g (550 mmol) of triethylamine are dissolved in 250 ml of dichloromethane, and the solution is cooled to 0° C. 59.75 g (550 mmol) of trimethylsilyl chloride are added dropwise, and the solution is stirred for 1 hour at room temperature and for 1 hour at 40° C. After cooling to −10° C., 26.64 g (250 mmol) of butyryl chloride are added dropwise, and the resulting mixture is stirred for 2 hours at −10° C. and for one hour at room temperature.

With ice-cooling, 125 ml of water are added dropwise, and the reaction mixture is stirred at room temperature for 15 minutes. The organic phase is admixed with aqueous sodium hydroxide solution and the organic solvent is removed under reduced pressure. After acidification, the precipitated solid is stirred once with water and twice with petroleum ether and dried at 45° C. under reduced pressure. This gives 29.1 g (67%) of a colourless solid.

200 MHz ¹H-NMR (DMSO-d6):0.88, 2t, 6H; 1.51, quart., 2H, 1.65, m, 2H, 2.09, t, 2H, 4.10, m, 1H; 8.01, d, 1H; 12.25, s, m 1H.

EXAMPLE 3A 2-Ethoxybenzonitrile

25 g (210 mmol) of 2-hydroxybenzonitrile are refluxed with 87 g of potassium carbonate and 34.3 g (314.8 mmol) of ethyl bromide in 500 ml of acetone overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 30.0 g (97%) of a colourless liquid.

200 MHz ¹H-NMR (DMSO-d6): 1.48, t, 3H; 4.15, quart., 2H; 6.99, dt, 2H; 7.51, dt, 2H.

EXAMPLE 4A 2-Ethoxybenzamidine hydrochloride

21.4 g (400 mmol) of ammonium chloride are suspended in 375 ml of toluene, and the suspension is cooled to 0° C. 200 ml of a 2M solution of trimethylaluminium in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. After addition of 29.44 g (200 mmol) of 2-ethoxybenzonitrile, the reaction mixture is stirred at 80° C. (bath) overnight.

With ice-cooling, the cooled reaction mixture is added to a suspension of 100 g of silica gel and 950 ml of chloroform, and the mixture is stirred at room temperature for 30 minutes. The mixture is filtered off with suction, and the filter residue is washed with the same amount of methanol. The mother liquor is concentrated, the resulting residue is stirred with a mixture of dichloromethane and methanol (9:1), the solid is filtered off with suction and the mother liquor is concentrated. This gives 30.4 g (76%) of a colourless solid.

200 MHz ¹H-NMR (DMSO-d6): 1.36, t, 3H; 4.12, quart., 2H; 7.10, t, 1H; 7.21, d, 1H; 7.52, m, 2H; 9.30, s, broad, 4H.

EXAMPLE 5A 2-Propoxybenzonitrile

75 g (630 ml) of 2-hydroxybenzonitrile are refluxed with 174 g (1.26 mol) of potassium carbonate and 232.2 g (1.89 mol) of ethyl bromide in 1 1 of acetone overnight. The solid is filtered off, the solvent is removed under reduced pressure and the residue is distilled under reduced pressure.

b.p.: 89° C. (0.7 mbar)

Yield: 95.1 g (93.7%)

EXAMPLE 6A 2-Propoxybenzamidine hydrochloride

21.41 g (400 mmol) of ammonium chloride are suspended in 400 ml of toluene and cooled to 0-5° C. 200 ml of a 2M solution of triethylaluminium in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. After addition of 32.2 g (200 mmol) of 2-propoxybenzonitrile, the reaction mixture is stirred at 80° C. (bath) overnight. With ice-cooling, the cooled reaction mixture is added to a suspension of 300 g of silica gel and 2.85 1 of ice-cooled chloroform, and the mixture is stirred for 30 minutes. The mixture is filtered off with suction and the filter residue is washed with the same amount of methanol. The solvent is distilled off under reduced pressure, the residue is stirred with 500 ml of a mixture of dichloromethane and methanol (9:1), the solid is filtered off and the mother liquor is concentrated. The residue is stirred with petroleum ether and filtered off with suction. This gives 22.3 g (52%) of product.

¹H-NMR (200 MHz, CD₃OD): 1.05 (3H); 1.85 (sex, 2H); 4.1 (A, 2H); 7.0-7.2 (m, 2H); 7.5-7.65 (m, 2H).

EXAMPLE 7A 2-Ethoxy-4-methoxybenzonitrile

30.0 g (201 mmol) of 2-hydroxy-4-methoxybenzonitrile are refluxed with 83.4 g of potassium carbonate (603 mmol) and 32.88 g (301 mmol) of bromoethane in 550 ml of acetone for 18 hours. After filtration, the solvent is removed under reduced pressure and the residue is purified by silica gel chromatography (cyclohexane:ethyl acetate=10:1): 35.9 g of an oil

R_(f)=0.37 (cyclohexane:ethyl acetate=3: 1)

200 MHz ¹H-NMR (CDCl₃): 1.48, t, 3H; 3.85, s, 3H; 4.12, quart., 2H; 6.46, m, 2H; 7.48, d, 1H.

EXAMPLE 8A 2-Ethoxy-4-methoxybenzamidine hydrochloride

6.98 g (130 mmol) of ammonium chloride are suspended in 150 ml of toluene, and the suspension is cooled to 0° C. 70 ml of a 2M solution of trimethylaluminium in hexane are added dropwise, and the mixture is stirred at room temperature until the evolution of gas has ceased. After addition of 11.56 g (65 mmol) of 2-ethoxy-4-methoxybenzonitrile, the reaction mixture is stirred at 80° C. (bath) overnight.

With ice-cooling, the cooled reaction mixture is added to a suspension of 100 g of silica gel and 950 ml of dichloromethane, and the mixture is stirred at room temperature for 30 minutes. The mixture is filtered off with suction and the filter residue is washed with the same amount of methanol. The mother liquor is concentrated, the resulting residue is stirred with a mixture of dichloromethane and methanol (9:1), the solid is filtered off with suction and the mother liquor is concentrated. The residue is stirred with petroleum ether and filtered off with suction. This gives 7.95 g (50%) of a solid.

200 MHz ¹H-NMR (DMSO-d6): 1.36, t, 3H; 3.84, s, 3H; 4.15, quart., 2H; 6.71, m, 2H; 7.53, d, 1H, 8.91, s, broad, 3H.

EXAMPLE 9A 2-(2-Ethoxyphenyl)-5,7-dimethyl-3H-imidazo[5, 1-f][1,2,4]triazin-4-one

24.4 g (0.186 mol) of N-acetyl-D,L-alanine are initially charged in 200 ml of absolute tetrahydrofuran, and 45 ml of absolute pyridine and 0.5 g of 4-dimethylaminopyridine are added. The mixture is heated to reflux, and 51.85 g (0.372 mol) of ethyl oxalyl chloride are added dropwise. The mixture is heated under reflux for a further 90 minutes, cooled, poured into ice-water and extracted three times with ethyl acetate. The organic phase is dried over sodium sulphate, concentrated and taken up in 62.5 ml of methanol. 9 g of sodium bicarbonate are added and the mixture is stirred under reflux for 2.5 hours and filtered.

With ice-cooling, 9.54 g (190.65 mmol) of hydrazine hydrate are added dropwise to a solution of 38.26 g (190.65 mmol) of 2-ethoxy-4-methoxybenzamidine hydrochloride in 250 ml of methanol, and the resulting suspension is stirred at room temperature for another 30 minutes. The methanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70° C. for 4 hours. After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.

The residue is taken up in 250 ml of 1,2-dichloroethane, 32.1 ml (348 mmol) of phosphorus oxychloride are added dropwise and the mixture is heated under reflux for two hours. The mixture is cooled, concentrated, taken up in a little methylene chloride and admixed with diethyl ether, and the solid is filtered off with suction. After the silica gel chromatography (methylene chloride/methanol 95:5), the solution is concentrated and the crystalline residue is stirred with diethyl ether.

Yield: 8.1 g (14.9% of theory)

200 MHz ¹H-NMR (CDCl₃): 1.58, t, 3H; 2.62, s, 3H; 2.68, s, 3H; 4.25, q, 2H; 7.04, d, 1H; 7.12, t, 1H; 7.5, dt, 1H; 8.19, dd, 1H; 10.02, s, 1H.

EXAMPLE 10A 2-(2-Ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

7.16 g (45 mmol) of 2-butyrylamino-propionic acid and 10.67 g of pyridine are dissolved in 45 ml of THF and, after addition of a spatula tip of DMAP, heated to reflux. 12.29 g (90 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours. The mixture is poured into ice-water and extracted three times with ethyl acetate and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 15 ml of ethanol and refluxed with 2.15 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.

With ice-cooling, 2.25 g (45 mmol) of hydrazine hydrate are added dropwise to a solution of 9.03 g (45 mmol) of 2-ethoxybenzamidine hydrochloride in 45 ml of ethanol, and the resulting suspension is stirred at room temperature for another 10 minutes. The ethanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70° C. for 4 hours. After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.

This residue is dissolved in 60 ml of 1,2-dichloroethane and, after addition of 7.5 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Chromatography using ethyl acetate and crystallization afford 4.00 g (28%) of a colourless solid, R_(f)=0.42 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.56, t, 3H; 1.89, hex, 2H; 2.67, s, 3H; 3.00, t, 2H; 4.26, quart., 2H; 7.05, m, 2H; 7.50, dt, 1H; 8.17, dd, 1H; 10.00, s, 1H.

EXAMPLE 11A 2-(2-Propoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

7.16 g (45 mmol) of 2-butyrylaminopropionic acid and 10.67 g of pyridine are dissolved in 45 ml of tetrahydrofuran and, after addition of a spatula tip of dimethylaminopyridine, heated to reflux. 12.29 g (90 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours. The mixture is poured into ice-water and extracted three times with ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 15 ml of ethanol and refluxed with 2.15 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.

With ice-cooling, 2.25 g (45 mmol) of hydrazine hydrate are added dropwise to a solution of 9.66 g (45 mmol) of 2-propoxybenzamidine hydrochloride in 45 ml of ethanol, and the resulting suspension is stirred at room temperature for another 10 minutes. The ethanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70° C. for 4 hours. After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is reduced under reduced pressure.

This residue is dissolved in 60 ml of 1,2-dichloroethane and, after addition of 7.5 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Crystallization from ethyl acetate gives 2.85 g (19.1%) of a yellow solid, chromatographic purification of the mother liquor gives a further 1.25 g (8.4%) of the product. R_(f)=0.45 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.03, t, 3H; 1.15, t, 3H; 1.92, m, 4H; 2.67, s, 3H; 3.01, t, 2H; 4.17, t., 2H; 7.09, m, 2H; 7.50, dt, 1H; 8.17, dd, 1H; 10.02, s, 1H.

EXAMPLE 12A 2-(2-Ethoxy-4-methoxyphenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

5.50 g (34.8 mmol) of 2-butyrylaminopropionic acid and 8.19 g of pyridine are dissolved in 35 ml of tetrahydrofuran and, after addition of a spatula tip of dimethylaminopyridine, heated to reflux. 9.43 g (69 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours. The mixture is poured into ice-water and extracted three times with ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 11 ml of methanol and refluxed with 1.65 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.

With ice-cooling, 1.73 g (34.5 mmol) of hydrazine hydrate are added dropwise to a solution of 7.95 g (34.5 mmol) of 2-ethoxy-4-methoxybenzamidine hydrochloride in 35 ml of ethanol, and the resulting suspension is stirred at room temperature for another 30 minutes. The methanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70° C. for 4 hours. After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.

This residue is dissolved in 46 ml of 1,2-dichloroethane and, after addition of 5.74 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Chromatography (dichloromethane:methanol=50:1) gives 0.31 g (2.5%) of a solid.

R_(f)=0.46 (dichloromethane:methanol=20:1)

200 MHz ¹H-NMR (CDCl₃): 1.03, t, 3H; 1.58, t, 3H; 1.88, m, 2H; 2.62, s, 3H; 2.98, t, 2H; 3.89, s, 3H; 4.25, quart., 2H; 6.54, d, 1H, 6.67, dd, 1H; 8.14, d, 1H; 9.54, s, 1H.

EXAMPLE 13A 2-(2-Ethoxyphenyl)-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

29.06 g (167.8 mmol) of 2-butyrylaminobutyric acid and 39.76 g of pyridine are dissolved in 170 ml of tetrahydrofuran and, after addition of a spatula tip of dimethylaminopyridine, heated to reflux. 45.81 g (335.5 mmol) of ethyl oxalyl chloride are slowly added dropwise, and the reaction mixture is refluxed for 3 hours. The mixture is poured into ice-water and extracted three times with ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. The residue is taken up in 15 ml of methanol, and half of the solution is refluxed with 7.96 g of sodium bicarbonate for 2.5 hours. The cooled solution is filtered.

With ice-cooling, 4.20 g (83.9 mmol) of hydrazine hydrate are added dropwise to a solution of 16.83 g (83.9 mmol) of 2-ethoxybenzamidine hydrochloride in 85 ml of ethanol, and the resulting suspension is stirred at room temperature for another 10 minutes. The methanolic solution described above is added to this reaction mixture, and the mixture is stirred at a bath temperature of 70° C. for 4 hours. After filtration, the mixture is concentrated, the residue is partitioned between dichloromethane and water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.

This residue is dissolved in 112 ml of 1,2-dichloroethane and, after addition of 14 ml of phosphorus oxychloride, refluxed for 2 hours. The mixture is diluted with dichloromethane and neutralized by addition of sodium bicarbonate solution and solid sodium bicarbonate. The organic phase is dried and the solvent is removed under reduced pressure. Chromatography (dichloromethane:methanol=50:1) gives 3.69 g (12.4%) of a colourless solid, R_(f)=0.46 (dichloromethane:methanol=20:1)

200 MHz ¹H-NMR (CDCl₃): 1.32, t, 3H; 1.57, t, 3H; 1.94, m, 8H; 3.03, quart., 2H; 3.64, quin., 1H; 4.27, quart., 2H; 7.06, d, 1H; 7.12, t, 1H; 7.50, dt, 1H, 8.16, dd, 1H; 9.91, s, 1H.

EXAMPLE 14A 4-Ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride

7.25 g (25.5 mmol) of 2-(2-ethoxyphenyl)-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]-triazin-4-one are initially charged, and 26.74 g (0.23 mol) of chlorosulphonic acid are added with ice-cooling. The mixture is stirred at room temperature overnight and poured into ice-water, and the crystals are filtered off with suction and dried in a vacuum desiccator.

Yield: 9.5 g (97% of theory)

200 MHz ¹H-NMR (d⁶-DMSO): 1.32, t, 3H; 2.63, s, 3H; 2.73, s, 3H; 4.13, q, 2H; 7.15, d, 1H; 7.77, m, 2H; 12.5, s, 1H;

EXAMPLE 15A 4-Ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride

At 0° C., 2.00 g (6.4 mmol) of 2-(2-ethoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are slowly added to 3.83 ml of chlorosulphonic acid. At room temperature, the reaction mixture is stirred overnight, and then poured into ice-water and extracted with dichloromethane. This gives 2.40 g (91%) of a colourless foam.

200 MHz ¹H-NMR (CDCl₃): 1.03, t, 3H; 1.61, t, 2H; 1.92, hex, 2H; 2.67, s, 3H; t, 2H; 4.42, quart., 2H; 7.27, t, 1H; 8.20, dd, 1H; 8.67, d, 1H; 10.18, s,

EXAMPLE 16A 4-Propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride

At 0° C., 2.80 g (8.6 mmol) of 2-(2-propoxy-phenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are added slowly to 5.13 ml of chlorosulphonic acid. The reaction mixture is stirred at room temperature overnight and then poured into ice-water and extracted with dichloromethane. This gives 3.50 g (96%) of a colourless foam.

R_(f)=0.49 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.03, 2t, 6H; 1.95, m, 4H; 2.81, s, 3H; 3.22, t, 2H; 4.11, t., 2H; 7.09, m, 1H; 8.06, dd, 1H; 8.21 m, 1H; 12.0, s, 1H.

EXAMPLE 17A 4-Ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride

At 0° C., 0.31 g (0.9 mmol) of 2-(2-ethoxy-4-methoxyphenyl)-5-methyl-7-propyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one are added slowly to 0.54 ml of chlorosulphonic acid. The reaction mixture is stirred at room temperature overnight and then poured into ice-water and extracted with dichloromethane. This gives 0.355 g (89%) of a colourless foam.

R_(f)=0.50 (dichloromethane/methanol=20:1)

200 MHz ¹H-NMR (CDCl₃): 1.05, t, 3H; 1.66, t, 3H; 1.95, m, 2H; 2.61, s, 3H, 3.11, t, 2H; 4.15, s, 3H; 4.40, quart., 2H; 6.65, s, 1H, 8.72, s, 1H; 9.75, s, 1H.

EXAMPLE 18A 4-Ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzene-sulphonyl chloride

At 0° C., 1.70 g (5.21 mmol) of 2-(2-ethoxy-phenyl)-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are added slowly to 3.12 ml of chlorosulphonic acid. The reaction mixture is stirred at room temperature overnight and then poured into ice-water and extracted with dichloromethane. This gives 2.10 g (94%) of a colourless foam.

400 MHz ¹H-NMR (CDCl₃): 1.03, t, 3H; 1.35, t, 3H; 1.62, t, 3H; 1.92, sex., 2H; 3.07, quart., 2H; 3.12, t, 2H; 4.42, quart., 2H; 7.38, d, 1H; 8.19, dd, 1H; 8.70, d, 1H; 10.08, s, broad, 1H.

EXAMPLE 19A Diethyl (4-piperidinylmethyl)-phosphonate

2.11 g (528 mmol) of 60% strength sodium hydride are initially charged in 50 ml of absolute tetrahydrofuran, and 15.7 g (52.8 mmol) of diethyl methanediphosphonate are added dropwise. The mixture is stirred at room temperature for another 30 minutes, and 10.1 g (52.8 mmol) of 1-benzyl-4-piperidone are then added. The mixture is stirred for one hour at room temperature and for one hour under reflux, concentrated, admixed with water and extracted three times with dichloromethane, and the organic phases are dried over sodium sulphate and concentrated. The residue is hydrogenated in 50 ml of ethanol over 1.7 g of 10% palladium-carbon at room temperature and 3 bar. The catalyst is filtered off with suction and the filtrate is concentrated.

Yield: 12.5 g (100% of theory)

400 MHz, ¹H-NMR (CDCl₃): 1.13, m, 2H; 1.32, t, 6H; 1.69, dd, 2H; 1.74-1.95m,, 4H; 2.62, dt, 2H; 3.05, m, 2H; 4.1, m, 4H.

EXAMPLE 20A 5-Methyl-4-furoxanecarbaldehyde

40 g (571 mmol) of crotonaldehyde are dissolved in 80 ml of acetic acid and, at 0° C., admixed dropwise with a solution of 137 g (1.99 mol) of sodium nitrite in 300 ml of water. The mixture is stirred at room temperature for 2 hours, diluted with 800 ml of water and extracted 3 times with dichloromethane. The organic phase is dried, and chromatography (cyclohexane/ethyl acetate) gives 13.8 g (18.9%) of 5-methyl-4-furoxanecarbaldehyde.

200 MHz ¹H-NMR (CDCl₃):2.39, s, 3H; 10.10, s, 1H.

EXAMPLE 21A 5-Methyl-4-furoxanecarbonyl chloride

13.5 g (105 mmol) of 5-methyl-4-furoxanecarbaldehyde are dissolved in 200 ml of acetone and, at 0° C., admixed dropwise with a solution of 16.86 g (168 mmol) of chromium trioxide in 120 ml of a 2.2M sulphuric acid. The mixture is stirred at 10-15° C. for 2 hours and then at room temperature overnight. With cooling, 100 ml of isopropanol are added dropwise and, after 30 minutes, the solvent is removed under reduced pressure. The aqueous phase is extracted 3 times with ether, the organic phase is dried over magnesium sulphate and the solvent is removed under reduced pressure. The residue is dissolved in 1M sodium hydroxide solution and the solution is extracted 3 times with ether. The aqueous phase is acidified and extracted 3 times with ether. The organic phase is dried and the solvent is removed under reduced pressure. The residue is stirred with petroleum ether and filtered off with suction.

6.92 g of the residue are refluxed with 10 ml of thionyl chloride in 20 ml of 5 dichloromethane for 6 hours. The mixture is diluted with toluene, filtered and concentrated using a rotary evaporator. The residue is once more taken up in dichloromethane, admixed with 10 ml of thionyl chloride and refluxed for 48 hours. The solvent is removed under reduced pressure and the residue is distilled under reduced pressure. This gives 2.00 g (25%) of colourless crystals.

200 MHz ¹H-NMR (CDCl₃): 2.41, s.

EXAMPLE 22A 1-(5-Methyl-4-furoxanecarbonyl)-4-tert-butyl-oxycarbonyl-piperazine

2.75 g (14.7 mmol) of Boc-piperazine and 1.49 g of triethylamine are dissolved in 20 ml of dichloromethane and, at 0° C., admixed a little at a time with 2.00 g (12.3 mmol) of 5-methyl-4-furoxanecarbonyl chloride. The mixture is stirred for 30 minutes at 0° C. and for 2 hours at room temperature, diluted with dichloromethane and washed with water. The solvent is removed under reduced pressure and the residue is purified by chromatography (cyclohexane/ethyl acetate). This gives 3.33 g (87%) of 1-(5-methyl-4-furoxanecarbonyl)-4-tert-butyl-oxycarbonyl-piperazine.

200 MHz ¹H-NMR (CDCl₃): 1.50, s, 9H; 2.30, s, 3H; 3.55, m, 4H; 3.78, m, 2H; 3.87, m, 2H.

EXAMPLE 23A 1-(5-Methyl-4-furoxanecarbonyl)-piperazine trifluoroacetate

3.12 g (10 mmol) of 1-(5-methyl-4-furoxanecarbonyl)-4-tert-butyl-oxycarbonyl-piperazine are dissolved in 20 ml of dichloromethane and, at 0° C., admixed with 2 ml of trifluoroacetic acid. The mixture is allowed to warm to room temperature and stirred for 72 hours. After addition of 10 ml of ether, the precipitate is filtered off with suction and dried. This gives 2.47 g (83%) of 1-(5-methyl-4-furoxanecarbonyl)-piperazine trifluoroacetate.

200 MHz ¹H-NMR (DMSO-d₆): 2.18, s, 3H; 3.18, m, 2H; 3.25, m, 2H; 3.83, m, 2H; 3.90, m, 2H; 8.89, s, broad, 2H.

PREPARATION EXAMPLES EXAMPLE 1 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

0.1 g (0.26 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo-[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 10 ml of dichloromethane and cooled to 0° C. After addition of a spatula tip of DMAP, 80 mg (0.784 mmol) of N-methylpiperazine are added and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with ammonium chloride solution and dried over sodium sulphate and the solvent is removed under reduced pressure. The residue is chromatographed over silica gel (dichloromethane/methanol 9:1).

Yield: 40 mg (34.5% of theory)

Mass spectrum: 447 (M+H); 284; 256; 224.

EXAMPLE 2 2-[2-Ethoxy-5-(4-hydroxyethylpiperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo [5,1-f][1,2,4] triazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.784 mmol) of 4-hydroxypiperazine, 45 mg (36.1% of theory) of 2-[2-ethoxy-5-(4-hydroxy-ethylpiperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one are obtained.

Mass spectrum: 477 (M+H); 284; 256; 239.

EXAMPLE 3 2-[2-Ethoxy-5-(4-hydroxypiperidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo [5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 80 mg (0.784 mmol) of 4-hydroxypiperidine, 35 mg (29.8% of theory) of 2-[2-ethoxy-5-(4-hydroxy-piperidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.61, t, 3H; 1.69, m, 2H; 1.94, m, 2H; 2.67, s, 3H; 2.70, s, 3H; 3.02, m, 2H; 3.30, m, 2H; 3.84, m, 1H; 4.37, q, 2H; 7.18, d, 1H; 7.90, dd, 1H; 8.52, d, 1H; 9.73, s, 1H.

EXAMPLE 4 2-[2-Ethoxy-5-(4-hydroxymethylpiperidine-1-sulphonyl)-phenyl] -5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 90 mg (0.784 mmol) of 4-hydroxymethylpiperidine, 22 mg (18% of theory) of 2-[2-ethoxy-5-(4-hydroxy-methylpiperidine-l-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.38, dt, 2H; 1.62, t, 3H; 1.82, dd, 2H; 2.35, dt, 2H; 2.78, s, 3H; 2.84, s, 3H; 3.5, d, 2H; 3.87, d, 2H; 4.39, q, 2H; 7.21, d, 1H; 7.95, dd, 1H; 8.51, d, 1H; 10.03, bs, 1H.

EXAMPLE 5 2-[2-Ethoxy-5-(3-hydroxypyrrolidine-I -sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 70 mg (0.784 mmol) of 3-hydroxypyrrolidine, 13 mg (11.1% of theory) of 2-[2-ethoxy-5-(3-hydroxy-pyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo-[5,1-f][1,2,4]triazin-4-one are obtained.

Mass spectrum: 434 (M+H)

EXAMPLE 6 4-Ethoxy-N-ethyl-N-(2-hydroxyethyl)-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f]-[1,2,4]triazin-2-yl)benzenesulphonamide

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 70 mg (0.784 mmol) of 2-(ethylamino)-ethanol, 23 mg (20.1% of theory) of 4-ethoxy-N-ethyl-N-(2-hydroxyethyl)-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo-[5,1-f][1,2,4] triazin-2-yl)-benzene-sulphonamide are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.2, t, 3H; 1.6, t, 3H; 2.17, bs, 1H; 2.69, s, 3H; 2.75, s, 3H; 3.33, m, 4H; 3.8, t, 2H; 4.36, q, 2H; 7.18, d, 1H; 7.99, dd, 1H; 8.6, d, 1H; 9.84, bs, 1H.

EXAMPLE 7 N,N-Diethyl-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo [5,1-f][1,2,4]triazin-2-yl)-benzene-sulphonyl chloride and 60 mg (0.784 mmol) of diethylamine, 21 mg (18.6% of theory) of N,N-diethyl-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.18, t, 6H; 1.61, t, 3H; 2.68, s, 3H; 2.72, s, 3H; 3.29, q, 4H; 4.35, q, 2H; 7.15, d, 1H; 7.95, dd, 1H; 8.58, d, 1H; 9.8, bs, 1H.

EXAMPLE 8 2-[2-Ethoxy-5-(4-(2-pyrimidinyl)-piperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo-[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (0.784 mmol) of 1-(2-pyrimidinyl)-piperazine, 38 mg (28.2% of theory) of 2-[2-ethoxy-5-(4-(2-pyrimidinyl)-piperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo-[5,1-f][1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.6, t, 3H; 2.68, s, 3H; 2.72, s, 3H; 3.12, t, 4H; 3.96, t, 4H; 4.34, q, 2H; 6.5, t, 1H; 7.18, d, 1H; 7.9, dd, 1H; 8.28, d, 2H; 8.51, d, 1H; 9.7, bs, 1H.

EXAMPLE 9 2-[2-Ethoxy-5-(morpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 70 mg (0.784 mmol) of morpholine, 28 mg (24.2% of theory) of 2-[2-ethoxy-5-(morpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.53, t, 3H; 2.69, s, 3H; 2.72, s, 3H; 3.06, t, 4H; 3.77, t, 4H; 4.39, q, 2H; 7.2, d, 1H; 7.91, dd, 1H; 8.51, d, 1H; 9.78, bs, 1H.

EXAMPLE 10 2-[2-Ethoxy-5-(1,4-dioxa-6-azaspiro[4.4]nonane-6-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.784 mmol) of 1,4-dioxa-6-azaspiro[4.4]nonane, 45 mg (35.3% of theory) of 2-[2-ethoxy-5-(1,4-dioxa-6-azaspiro[4.4]nonane-6-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]-triazin-4-one.

200 MHz ¹H-NMR (CDCl₃): 1.58, t, 3H; 2.02, t, 2H; 2.61, s, 3H; 2.65, s, 3H; 3.32, s, 2H; 3.41, t, 2H; 3.88, m, 4H; 4.34, q, 2H; 7.17, d, 1H; 7.92, dd, 1H; 8.51, d, 1H; 9.92, bs, 1H.

EXAMPLE 11 N,N-Bis-(2-methoxyethyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f]-[1,2,4]triazin-2-yl)-benzenesulphonamide

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzene-sulphonyl chloride and 100 mg (0.784 mmol) of bis-(2-methoxyethyl)-amine, 37 mg (27.5% of theory) of N,N-bis-(2-methoxy-ethyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.

200 MHz ¹H-NMR (CDCl₃):1.58, t, 3H; 2.61, s, 3H; 2.64, s, 3H; 3.3, s, 6H; 3.46, t, 4H; 3.56, t, 4H; 4.32, q, 2H; 7.12, d, 1H; 7.95, dd, 1H; 8.51, d, 1H; 9.9, bs, 1H

EXAMPLE 12 N-(3-Isoxazolyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 70 mg (0.784 mmol) of 3-aminoisoxazol, 20 mg (17.2% of theory) N-(3-isoxazolyl)-4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.

200 MHz ¹H-NMR (CDCl₃): 1,6, t, 3H; 2.73, s, 3H; 2.81, s, 3H; 4.35, q, 2H; 6.6, d, 1H; 7.14, d, 1H; 8.05, dd, 1H; 8.27, d, 1H; 8.63, d, 1H; 9.61, bs, 1H.

EXAMPLE 13 2-[2-Ethoxy-5-(2-t-butoxycarbonylaminomethylmorpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 170 mg (0.784 mmol) of 2-t-butoxycarbonyl-aminomethylmorpholine, 64 mg (42.2% of theory) of 2-[2-ethoxy-5-(2-t-butoxycarbonylaminomethylmorpholine-4-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

Mass spectrum: 563 (M+H)

EXAMPLE 14 2-[2-Ethoxy-5-(4-phenylpiperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (0.784 mmol) of 1-phenylpiperazine, 38 mg (28.3% of theory) of 2-[2-ethoxy-5-(4-phenylpiperazine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (CDCl₃):1.62, t, 3H; 2.72, s, 3H; 2.77, s, 3H; 3.25, m, 8H; 4.38, q, 2H; 6.92, m, 2H; 7.02, d, 1H; 7.18-7.37, m, 3H; 7.94, dd, 1H; 8.55, m, 1H; 9.79, bs, 1H.

EXAMPLE 15 2-[2-Ethoxy-5-(3-hydroxy-3-methoxymethylpyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.261 mmol) of 4-ethoxy-3-(5,7-dimethyl-4-oxo-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.784 mmol) of 3-hydroxy-3-methoxymethylpyrrolidine, 30 mg (23.5% of theory) of 2-[2-ethoxy-5-(3-hydroxy-3-methoxymethylpyrrolidine-1-sulphonyl)-phenyl]-5,7-dimethyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

Mass spectrum: 478 (M+H)

EXAMPLE 16 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

1.23 g (3 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 40 ml of dichloromethane and cooled to 0° C. After addition of a spatula tip of DMAP, 0.90 g (9.00 mmol) of N-methylpiperazine are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed twice with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 1.25 g (88%) of a colourless solid.

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.59, t, 3H; 1.88, hex, 2H; 2.29, s, 3H; 2.51, m, 4H; 2.63, s, 3H; 3.00, t, 2H; 3.08, m, 4H; 4.33, quart., 2H, 7.17, d, 1H; 7.88, dd, 1H; 8.44, d, 1H; 9.75, s, 1H.

EXAMPLE 17 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one lactate

100 mg (0.211 mmol) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are suspended in 5 ml of ether and admixed with 20 mg of an 85% strength solution of lactic acid in water. The mixture is stirred at room temperature for 10 minutes and evaporated to dryness. The residue is titrated with ether and filtered off with suction. This gives 110 mg (92%) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one lactate.

200 MHz ¹H-NMR (DMSO-d₆): 0.92, t, 3H; 1.22, d, 3H; 1.31, t, 3H; 1.74, m, 1H; 2.15, s, 3H; 2.38, m, 4H; 2.81, t, 2H; 2.91, m, 4H; 4.05, quart., 1H; 4.21, quart., 2H; 7.40, d, 1H; 7.85, m, 2H; 11.71, s, broad, 1H.

EXAMPLE 18 2-[2-Ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride

100 mg (0.211 mmol) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are suspended in 5 ml of diethyl ether, admixed with 0.23 ml of a 1M solution of HCl in ether and stirred at room temperature for 15 minutes. The solvent is removed under reduced pressure. This gives 107 mg (97%) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride.

200 MHz ¹H-NMR (DMSO-d₆): 0.93, t, 3H; 1.35, t, 3H; 1.75, sex., 2H; 2.72, s, 3H; 2.86, m, 4H; 3.15, m, 2H; 3.45, m, 2H; 3.81, m, 2H; 4.25, quart., 2H; 7.45, d, 1H; 7.95, m, 2H; 11.39, s, 1H; 11.90, s, 1H.

EXAMPLE 19 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

470 mg (1.14 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 20 ml of dichloromethane and cooled to 0° C. 390 mg (3.42 mmol) of N-ethylpiperazine are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed twice with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 370 mg (66%) of a colourless solid.

400 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.59, t, 3H; 1.88, hex, 2H; 2.42, quart., 2H; 2.56, m, 4H; 2.63, s, 3H; 3.00, t, 2H; 3.10, m, 4H; 4.33, quart., 2H, 7.17, d, 1H; 7.88, dd, 1H; 8.44, d, 1H; 9.75, s, 1H.

EXAMPLE 20 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride

0.35 g (0.712 mmol) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are suspended in 8 ml of ether and dichloromethane is added until a homogeneous solution is formed. 0.8 ml of a 1M solution of HCl in ether is added, and the mixture is stirred at room temperature for 20 minutes and filtered off with suction. This gives 372 mg (99%) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride.

200 MHz ¹H-NMR (DMSO-d₆): 0.96, t, 3H; 1.22, t, 3H; 1.36, t, 3H; 1.82, sex., 2H; 2.61, s, 3H; 2.88, m, 2H; 3.08, m, 6H; 3.50, m, 2H; 3.70, m, 2H; 4.25, quart., 2H; 7.48, d, 1H; 7.95, m, 2H; 11.42, s, 1H; 12.45, s, 1H.

EXAMPLE 21 2-[2-Ethoxy-5-(4-methyl-1-amino-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.03 g (0.29 mmol) of 1-amino-4-methylpiperazine, 40 mg (83%) of 2-[2-ethoxy-5-(4-methyl-1-amino-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.09 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.59, t, 3H; 1.90, sex., 2H; 2.22, s, 3H; 2.40, m, 4H; 2.62, s, 3H; 2.71, m, 4H; 3.00, m, 2H; 4.32, quart., 2H; 7.14, d, 1H; 8.05, dd, 1H; 8.60, d, 1H.

EXAMPLE 22 2-[2-Ethoxy-5-(4-hydroxyethyl-1-amino-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.04 g (0.29 mmol) of 1-amino-4-hydroxyethylpiperazine, 46 mg (91%) of 2-[2-ethoxy-5-(4-hydroxyethyl-1-amino-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.08 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.59, t, 3H; 1.90, sex., 2H; 2.49, m, 6H; 2.62, s, 3H; 2.71, m, 4H; 3.00, t, 2H; 3.55, t, 2H; 4.31, quart., 2H; 7.14, d, 1H; 8.05, dd, 1H; 8.60, d, 1H.

EXAMPLE 23 2-[2-Ethoxy-5-(N,N-bishydroxyethyl-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.04 g (0.29 mmol) of 1-amino-4-hydroxyethylpiperazine, 46 mg (91%) of 2-[2-ethoxy-5-(N,N-bishydroxyethyl-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.08 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.53, t, 3H; 1.70, m, 2H; 1.86, sex., 2H; 2.9, m, 9H; 2.95, t, 2H; 3.09, t, 2H; 3.65, t, 4H; 4.28, quart., 2H; 7.14, d, 1H; 7.95, dd, 1H; 8.35, d, 1H.

EXAMPLE 24 2-[2-Ethoxy-5-(4-dimethoxyphosphorylmethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 0.4 g (0.97 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride, 390 mg of triethylamine and 0.86 g (2.99 mmol) of 4-dimethoxyphosphorylmethyl-piperazine trifluoroacetate, 321 mg (53%) of 2-[2-ethoxy-5-(4-dimethoxyphosphoryl-methyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.4 (dichloromethane/methanol=20:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.60, t, 3H; 1.88, sex., 2H; 2.62, s, 3H; 2.75, m, 4H; 3.02, t, 2H; 3.11, m, 4H; 3.70, s, 3H; 3.75, s, 3H; 4.35, quart., 2H; 5.30, s, 2H; 7.18, d, 1H; 7.88, dd, 1H; 8.45, d, 1H; 9.71, s, 1H.

EXAMPLE 25 2-[2-Ethoxy-5-(4-diethoxyphosphorylmethyl-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 0.4 g (0.97 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.86 g (3.7 mmol) of 4-diethoxyphosphorylmethyl-piperidine, 366 mg (49%) of 2-[2-ethoxy-5-(4-diethoxyphosphorylmethyl-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.4 (dichloromethane/methanol=20:1)

200 MHz ¹H-NMR (DMSO-d₆): 0.92, t, 3H; 1.20, t, 6H; 1.35, t, 3H; 1.75, m, 7H; 2.25, m, 2H; 2.82, t, 2H; 3.61, d, 2H; 3.95, quin., 4H; 4.21, quart., 2H; 7.38, d, 1H; 7.87, m, 2H; 11.70, s, 1H.

EXAMPLE 26 2-[2-Ethoxy-5-(4-hydroxy-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 531 mg (1.29 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 393 mg (3.88 mmol) of 4-hydroxypiperidine, 400 mg (64%) of 2-[2-ethoxy-5-(4-hydroxy-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (DMSO-d6): 0.941, t, 3H; 1.32, t, 3H; 1.45, m, 2H; 1.71, m, 4H; 2.48, s, 3H; 2.82, m, 4H; 3.11,m, 2H; 3.55, m, 1H; 4.20, quart., 2H; 4.72, d, 1H, 7.39, d,1H; 7.87, m, 2H; 11.70, s, 1H.

EXAMPLE 27 2-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 411 mg (1 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 391 mg (3 mmol) of 4-hydroxyethylpiperazine, 380 mg (75%) of 2-{2-ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.198 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.87, hex., 3H; 2.60, m, 7H; 3.00, t, 2H; 3.10, m, 4H; 3.60, t, 2H; 4.36, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 28 2-{2-Ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride

200 mg (0.39 mmol) of 2-{2-ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are suspended in ether, admixed with 2 ml of a 1M solution of HCl in ether and stirred at room temperature for 20 minutes. The solvent is removed, giving 209 mg (100%) of 2-{2-ethoxy-5-[4-(2-hydroxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride.

200 MHz ¹H-NMR (DMSO-d6): 0.96, t, 3H; 1.35, t, 3H; 1.70, sex., 2H; 2.59, s, 3H; 2.85, t, 2H; 2.99, t, 2H; 3.18, m, 4H; 3.59, d, 2H; 3.75, m, 4H; 4.25, quart., 2H; 7.49, d, 1H; 7.95, m, 2H; 10.62, s, 1H; 12.31, s, 1H.

EXAMPLE 29 2-{2-Ethoxy-5-[4-(3-hydroxy-propyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 150 mg (0.37 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 158 mg (1.09 mmol) of 4-(3-hydroxypropyl)-piperazine, 167 mg (83%) of 2-{2-ethoxy-5-[4-(3-hydroxy-propyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.52 (dichloromethane/methanol=10:1)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.70, m, 5; 2.62 m, 8H; 3.00, t, 2H; 3.10, m, 4H; 3.72, t, 2H; 4.36, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 30 N-Allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide

By the same method, starting with 420 mg (1.02 mmol) (1 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 300 mg (3 mmol) of allylhydroxyethylamine, 400 mg (82%) of N-allyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide are obtained.

R_(f)=0.345 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.90, m, 2H; 2.22, s, broad, 1H; 2.62, s, 3H; 2.99, t, 2H; 3.31, t, 2H; 3.78, t, 2H; 3.92, d, 2H; 4.37, quart., 2H; 5.23, m, 2H; 5.71, m, 1H; 7.15, d, 1H; 7.98, dd, 1H; 8.56, d, 1H; 9.66, s, 1H.

EXAMPLE 31 N-Ethyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide

By the same method, starting with 411 mg (1.0 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 267 mg (3 mmol) of ethylhydroxyethylamine, 325 mg (70%) of N-ethyl-4-ethoxy-N-(2-hydroxy-ethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide are obtained.

R_(f)=0.29 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.20, t, 3H; 1.61, t, 3H; 1.88, sex., 2H; 2.30, s, broad, 1H; 2.62, s, 3H; 2.99, t, 2H; 3.32, m, 4H; 3.78, t, 2H; 3.80, m, 2H; 4.37, quart., 2H; 7.15, d, 1H; 7.98, dd, 1H; 8.56, d, 1H; 9.70, s, 1H.

EXAMPLE 32 N,N-Diethyl-4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide

By the same method, starting with 400 mg (0.97 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 210 mg (2.92 mmol) of diethylamine, 398 mg (89%) of N,N-diethyl-4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide are obtained.

R_(f)=0.49 (dichloromethane/methanol=20:1)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.20, t, 6H; 1.49, t, 1.61, t, 3H; 1.88, sex., 2H; 2.30, s, broad, 1H; 2.62, s, 3H; 2.99, t, 2H; 3.32, m, 4H; 3.78, t, 2H; 3.80, m, 2H; 4.37, quart., 2H; 7.15, d, 1H; 7.98, dd, 1H; 8.56, d, 1H; 9.70, s, 1H.

EXAMPLE 33 N-(2-Methoxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide

By the same method, starting with 1.23 g (3 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 680 mg (9 mmol) of 2-methoxyethylamine, 900 mg (67%) of N-(2-methoxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-benzenesulphonamide are obtained.

R_(f)=0.25 (dichloromethane/methanol=95:5)

400 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.58, t, 3H; 1.88, sex., 2H; 2.62, s, 3H; 3.01, t, 2H; 3.18, quart., 2H; 3.30, s, 3H; 3.45, t, 2H; 4.32, quart., 2H; 5.12, t, 1H; 7.13, d, 1H, 7.97, dd, 1H, 8.53, d, 1H; 9.82, s, 1H.

EXAMPLE 34 N-(2-N,N-Dimethylethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide

By the same method, starting with 210 mg (0.49 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (9 mmol) of 2-N,N-dimethylethylamine, 150 mg (59%) of N-(2-N,N-dimethylethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide are obtained.

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.62, m, 4H; 1.88, sex., 2H; 2.11, s, 6H; 2.39, t, 2H; 2.63, s, 3H; 3.01, m, 3H; 4.38, quart., 2H; 7.13, d, 1H, 7.97, dd, 1H, 8.53, d, 1H; 9.82, s, 1H.

EXAMPLE 35 N-[3-(1-Morpholino)propyl]-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide

By the same method, starting with 1.23 g (3 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 1.3 g (9 mmol) of 3-(1-morpholino)-propylamine, 1.38 g (88%) of N-[3-(1-morpholino)propyl]-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide are obtained.

R_(f)=0.23 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.58, t, 3H; 1.72, m, 2H; 1.88, sex., 2H; 2.46, m, 6H; 2.62, s, 3H; 3.01, t, 2H; 3.15, t, 2H; 3.71, t, 4H; 4.32, quart., 2H; 7.13, d, 1H, 7.97, dd, 1H, 8.53, d, 1H; 9.79, s, 1H.

EXAMPLE 36 N-{3-[1-(4-Methyl)piperazino]-propyl}-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide

By the same method, starting with 0.04 g (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 0.05 g (0.29 mmol) of 3-[1-(4-methyl-)piperazino]-propylamine, 0.04 g (77%) of N-{3-[1-(4-methyl)piperazino]-propyl}-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-benzenesulphonamide is obtained.

R_(f)=0.11 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.55, t, 3H;1.68, m, 2H; 1.88, sex., 2H; 2.27, s, 3H; 2.45, m, 8H; 2.62, s, 3H; 2.98, m, 3H; 3.10, t, 2H; 3.46, s, 1H; 4.30, quart., 2H; 7.13, d, 1H, 7.97, dd, 1H, 8.53, d, 1H.

EXAMPLE 37 2-{2-Ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 40 mg (0.29 mmol) of 4-methoxyethylpiperazine, 50 mg (99%) of 2-{2-ethoxy-5-[4-(2-methoxy-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.27 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.87, hex., 3H; 2.60, m, 9H; 2.97, t, 2H; 3.10, m, 4H; 3.60, s, 3H; 3.46, t, 2H; 4.36, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 38 2-{2-Ethoxy-5-[4-(2-N,N-dimethyl-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 50 mg (0.29 mmol) of 4-(2-N,N-dimethyl)-ethylpiperazine, 50 mg (99%) of 2-{2-ethoxy-5-[4-(2-N,N-dimethyl-ethyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.11 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.87, hex., 3H; 2.20, s, 6H; 2.42, m, 4H; 2.58, m, 4H; 2.63, s, 3H; 2.99, m, 3H; 3.10, m, 4H; 4.36, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 39 2-{2-Ethoxy-5-[4-(3-N,N-dimethyl-propyl)-piperazin-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.243 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 130 mg (0.73 mmol) of 4-(3-N,N-dimethyl)-propylpiperazine, 72 mg (54%) of 2-{2-ethoxy-5-[4-(3-N,N-dimethyl-propyl)-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.08 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.87, sex., 3H; 2.20, s, 6H; 2.25, m, 2H; 2.38, t, 2H; 2.52, m, 4H; 2.63, s, 3H; 2.99, m, 6H; 4.33, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 40 2-[2-Ethoxy-5-(4-dioxolano-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 100 mg (0.243 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 100 mg (0.73 mmol) of 4-dioxolanopiperidine, 111 mg (88%) of 2-[2-ethoxy-5-(4-dioxolano-piperidine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.80, m, 6H; 2.63, s, 3H; 2.99, t, 2H; 3.20, m, 4H; 3.90, s, 4H; 4.33, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 41 2-[2-Ethoxy-5-(4-(5-methyl-4-furoxanecarbonyl)-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

410 mg (1.0 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 10 ml of dichloromethane and cooled to 0° C. 590 mg (2.00 mmol) of 1-(5-methyl-4-furoxanecarbonyl)-piperazine trifluoroacetate and 400 mg of triethylamine are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with ammonium chloride solution, 1M hydrochloric acid and water and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 448 mg (74%) of a colourless solid.

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.59, t, 3H; 1.88, hex, 2H; 2.25, s, 3H; 2.63, s, 3H; 3.00, t, 2H; 3.20, m, 4H; 3.90, m, 2H; 4.02, m, 2H; 4.33, quart., 2H, 7.19, d, 1H; 7.89, dd, 1H; 8.48, d, 1H; 9.57, s, 1H.

EXAMPLE 42 2-{2-Ethoxy-5-[4-acetyl-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 40 mg (0.29 mmol) of N-acetylpiperazine, 9 mg (18%) of 2-{2-ethoxy-5-[4-acetyl-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.34 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.87, sex., 3H; 2.05, s, 3H; 2.63, s, 3H; 3.00, m, 6H; 3.59, m, 2H; 3.72, m, 2H; 4.33, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H, 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 43 2-{2-Ethoxy-5-[4-formyl-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 40 mg (0.097 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 30 mg (0.29 mmol) of N-formylpiperazine, 35 mg (73%) of 2-{2-ethoxy-5-[4-formyl-piperazine-1-sulphonyl]-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.29 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.61, t, 3H; 1.87, sex., 3H; 2.05, s, 3H; 2.63, s, 3H; 3.00, m, 6H; 3.50, m, 2H; 3.69, m, 2H; 4.33, quart., 2H; 7.18, d, 1H, 7.89, dd, 1H; 8.00, s, 1H; 8.47, d, 1H, 9.71, s, 1H.

EXAMPLE 44 2-[2-Ethoxy-5-(3-butylsydnoneimine)-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

110 mg (0.6 mmol) of 3-butylsydnoneimine hydrochoride are dissolved in 2.5 ml of pyridine and cooled to 0° C. 210 mg (0.5 mmol) of 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are added, and the reaction mixture is stirred for 2 hours at 0° C. and overnight at room temperature. The mixture is diluted with dichloromethane, the organic phase is washed with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Chromatography (dichloromethane/methanol) gives 16 mg (6%) of 2-[2-ethoxy-5-(3-butylsydnoneimine)-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one.

R_(f)=0.41 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.01, 2t, 6H; 1.47, sex., 2H; 1.55, t, 3H; 1.88, m, 2H; 2.04, quin., 2H; 2.62, s, 3H; 2.98, t, 2H; 4.29, quart., 2H; 4.41, t, 2H; 7.08, d, 1H; 7.56, s, 1H; 7.98, dd, 1H; 8.58, d, 1H; 9.79, s, broad, 1H.

EXAMPLE 45 5-Methyl-2-[5-(4-methyl-piperazine-1-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

0.85 g (2 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]-triazin-2-yl)-benzenesulphonyl chloride are dissolved in 20 ml of dichloromethane and cooled to 0° C. After addition of a spatula tip of DMAP, 0.60 g (6.00 mmol) of N-methylpiperazine is added and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with ammonium chloride solution and dried over sodium sulphate and the solvent is removed under reduced pressure. Crystallization from ether gives 0.80 g (77%) of a colourless solid.

R_(f)=0.233 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.00, t, 3H; 1.15, t, 3H; 1.87, hex, 2H; 1.99, hex., 2H; 2.30, s, 3H; 2.52, m, 4H; 2.62, s, 3H; 2.99, t, 2H; 3.10, m, 4H; 4.21, t, 2H; 7.17, d, 1H; 7.87, dd, 1 h, 8.48, d, 1H, 9.70, s, 1H.

EXAMPLE 46 5-Methyl-2-[5-(4-methyl-piperazine-1-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride

22 mg (0.045 mmol) of 5-methyl-2-[5-(4-methyl-piperazine-1-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are dissolved in 2 ml of ether and 1 ml of dichloromethane and admixed with 0.1 ml of a 1M solution of HCl in ether. After 20 minutes, the precipitate is filtered off with suction and dried.

200 MHz ¹H-NMR (CDCl₃): 0.95, t, 3H; 1.75, m, 2H; 2.56, s, 3H; 2.75, m, 4H; 2.97, t, 2H; 3.15, m, 2H; 3.44, m, 2H; 3.81, m, 2H; 4.15, t, 2H; 7.47, d, 1H; 7.95, m, 2H; 11.12, s, 1H; 12.22, s, 1H.

EXAMPLE 47 2-[5-(4-Hydroxypiperidine-1-sulphonyl)-2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 850 mg (2 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 610 mg (6 mmol) of 4-hydroxypiperidine, 736 mg (75%) of 2-[5-(4-hydroxypiperidine-1-sulphonyl)-2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.07 (dichloromethane/methanol=95:5)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.16, t, 3H; 1.80, m, 9H; 2.65, s, 3H; 3.00, m, 4H; 3.32, m, 2H; 3.85,m, 1H; 4.22, t., 2H; 7.17, d,1H; 7.89, dd, 1H; 8.50, d, 1H; 11.70, s, 1H.

EXAMPLE 48 2-[5-(4-Hydroxymethylpiperidine-1-sulphonyl)-2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 35 mg (0.3 mmol) of 4-hydroxymethylpiperidine, 41 mg (82%) of 2-[5-(4-hydroxymethylpiperidine-1-sulphonyl)-2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.52 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.001, t, 3H; 1.16, t, 3H; 1.60, m, 4H; 1.82, m, 5H; 2.31, t, 2H, 2.62, s, 3H, 2.98, t, 2H, 3.48, d, 2H; 3.85, d, 2H; 4.21, t, 2H; 7.17, d, 1H; 7.88, dd, 1H, 8.45, d, 1H; 9.71, s, 1H.

EXAMPLE 49 2-{5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-2-propoxy-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 39 mg (0.3 mmol) of 4-hydroxymethylpiperazine, 50 mg (96%) of 2-{5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-2-propoxy-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.43 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.15, t, 3H, 1.88, m, 2H, 2.00, m, 2H, 2.62, m, 9H, 3.00, t, 2H, 3.07, m, 4H, 3.58, t, 2H, 4.23, t, 2H; 7.19, d, 1H; 7.88, dd, 1H, 8.43, d, 1H, 9.85, s, 1H.

EXAMPLE 50 N-(1,1-Dioxotetrahydro-1λ⁶-thiophene-3-yl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo-[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 41 mg (0.3 mmol) of 2-aminosulpholane, 8 mg (14%) of N-(1,1-dioxotetrahydro-1λ⁶-thiophene-3-yl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo-[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.49 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.15, t, 3H, 1.85, m, 2H; 1.99, m, 2H; 2.30, m, 1H; 2.50, m, 1H; 2.62, s, 3H; 2.95, m, 4H; 3.21, m, 1H; 4.20, m, 3H; 5.98, s, 1H; 7.18, d, 1H, 7.98, dd, 1H; 8.51,d, 1H, 9.71, s, 1H.

EXAMPLE 51 N-(2-Dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.3 mmol) of 1,1,4-trimethyldiaminoethane, 39 mg (79%) of N-(2-dimethylaminoethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.28 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.15, t, 3H, 1.88, m, 2H; 2.01, m, 2H; 2.25, s, 6H; 2.50, t, 2H; 2.62, s, 3H; 2.82, s, 3H; 3.01, t, 2H; 3.18, t, 2H; 4.21, t, 2H; 7.16, d, 1H, 7.91, dd, 1H, 8.50, d, 1H; 9.70, s, 1H.

EXAMPLE 52 3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 43 mg (0.3 mmol) of 1-(3-aminopropyl)-morpholine, 52 mg (97%) of 3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.33 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H, 1.15, t, 3H, 1.71, m, 2H; 1.93, m, 4H; 2.43, m, 6H; 2.62, s, 3H; 2.98, t, 2H; 3.12, t, 2H; 3.70, m, 4H; 4.21, t, 2H; 7.15, d, 1H; 7.96, dd, 1H; 8.55, d, 1H; 9.85, s, 1H.

EXAMPLE 53 N,N-Bis-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 32 mg (0.3 mmol) of bishydroxyethylamine, 34 mg (69%) of N,N-bis-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.36 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.15, t, 3H; 1.85, m, 2H; 1.97, m, 2H; 2.60, s, 3H; 2.98, t, 2H; 3.33, t, 4H; 3.87, t, 4H; 4.20, t, 2H; 7.15, d, 1H; 7.92, dd, 1H; 8.49, d, 1H; 9.85, s, 1H.

EXAMPLE 54 N-(3-Hydroxybenzyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 37 mg (0.3 mmol) of 3-hydroxybenzylamine, 4 mg (8%) of N-(3-hydroxybenzyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.43 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃):1.01, t, 3H, 1.13, t, 3H; 1.83, m, 2H; 1.96, m, 2H; 2.59, s, 3H, 2.96, t, 2H, 4.16, m, 4H, 5.05, t, 1H; 6.52, s, 1H; 6.70, m, 2H; 7.06, m, 2H; 7.93, dd, 1H, 8.41, d, 1H, 9.77, s, 1H.

EXAMPLE 55 N-Ethyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 27 mg (0.3 mmol) of ethylhydroxyethylamine, 18 mg (38%) of N-ethyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.48 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃):1.01, t, 3H; 1.15, 2t, 6H; 1.75, s, 2H; 1.85, m, 2H; 1.98, m, 2H; 2.40, s, 1H; 2.62, s, 3H; 2.99, t, 2H; 3.32, m, 4H; 3.90, quart., 2H, 4.21, quart., 2H; 7.15, d, 1H; 7.95, dd, 1H; 8.55, d, 1H, 9.73, s, 1H.

EXAMPLE 56 N-(3-Ethoxypropyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.3 mmol) of 3-ethoxypropylamine, 47 mg (96%) of N-(3-ethoxypropyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.60 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.15, m, 6H; 1.89, m, 7H; 2.62, s, 3H; 3.00, t, 2H; 3.12, quart., 2H; 3.46, m, 4H; 4.20, t, 2H; 5.52, m, 1H; 7.15, d, 1H; 7.98, dd, 1H; 8.55, d, 1H, 9.85, s, 1H.

EXAMPLE 57 2-[5(4-Hydroxypiperidine-1-sulphonyl)2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 212 mg (0.5 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 152 mg (1.5 mmol) of 4-hydroxypiperidine, 125 mg (50%) of 2-[5(4-hydroxypiperidine-1-sulphonyl)2-propoxy-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.07 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 1.05, t, 3H; 1.18, t, 3H, 1.98, m, 8H, 2.71, s, 3H; 3.10, m, 2H; 3.28, m, 4H; 3.88, m, 1H; 4.28, t, 2H; 7.21, d, 1H; 7.97, dd, 1H, 8.45, d, 1H. 10.45, s, 1H.

EXAMPLE 58 3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-N-pyridin-4-yl-benzenesulphonamide

By the same method, starting with 85 mg (0.2 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 56 mg (0.6 mmol) of 4-aminopyridine, 24 mg (25%) of 3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-N-pyridin-4-yl-benzenesulphonamide are obtained after 18 hours at reflux in 1 ml of THF.

R_(f)=0.13 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃+CD₃OD): 1.01, t, 3H; 1.09, t, 3H; 1.90, m, 4H; 2.60, s, 3H; 2.99, t, 2H; 4.16, t, 2H; 7.05, d, 2H; 7.15, d, 1H; 7.88, d, 2H; 8.05, dd, 1H; 8.41, d, 1H.

EXAMPLE 59 N,N-Diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 22 mg (0.6 mmol) of diethylamine, 42 mg (92%) of N,N-diethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.64 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.18, 2t, 9H; 1.92, 2 hex., 4H; 2.62, s, 3H; 3.00, t, 2H, 3.29, quart., 4H; 4.21, t, 2H; 7.13, d, 1H; 7.93, dd, 1H, 8.51, d, 1H, 9.85, s, 1H.

EXAMPLE 60 1-[3-(5-Methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonyl]-piperidine-4-carboxylic acid

By the same method, starting from 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 14 mg (0.6 mmol) of piperidinecarboxylic acid in 1 ml of a mixture of THF and water (1:1) with 26.5 mg of sodium carbonate, 21 mg (41%) of 1-[3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonyl]-piperidine-4-carboxylic acid are obtained.

R_(f)=0.28 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 0.90, t, 3H; 1.04, t, 3H; 1.80, m, 4H; 2.21, m, 2H, 2.51, s, 3H, 2.85, m, 2H, 3.56, m, 6H; 4.10, t, 2H; 7.12, d, 1H, 7.71, dd, 1H, 8.10, d, 1H, 10.72, s, broad, 1H.

EXAMPLE 61 5-Methyl-2-[5-(morpholine-4-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 26 mg (0.3 mmol) of morpholine, 34 mg (71%) of 5-methyl-2-[5-(morpholine-4-sulphonyl)-2-propoxy-phenyl]-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.64 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.16, t, 3H, 1.89, hex., 2H, 2.00, hex., 2H; 2.63, s, 3H; 3.02, m, 4H; 4.25, t, 2H, 7.19, d, 1H, 7.89, dd, 1H; 8.48, d, 1H; 9.78, s, 1H.

EXAMPLE 62 N-(2-Hydroxyethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 23 mg (0.63 mmol) of methylhydroxyethylamine, 25 mg (54%) of N-(2-hydroxyethyl)-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.53 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.15, t, 3H; 1.82, m, 2H; 1.99, hex., 2H; 2.40, s, broad, 1H, 2.62, s, 3H, 2.89, s, 3H; 2.99, t, 2H; 3.21, t, 2H; 3.80, s, broad, 2H; 4.21, t, 2H, 7.16, d, 1H; 7.92, dd, 1H, 8.50, d, 1H, 9.79, s, 1H.

EXAMPLE 63 N-(2-Hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-N-propyl-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.6 mmol) of propylhydroxyethylamine, 20 mg (40%) of N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]-triazin-2-yl)-4-propoxy-N-propyl-benzenesulphonamide are obtained.

R_(f)=0.52 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃): 0.90, t, 3H; 1.01, t, 3H; 1.15, t, 3H; 1.52, m, 2H, 1.88, m, 2H, 2.00, m, 2H; 2.40, s, 1H; 2.63, s, 3H, 3.01, t, 2H, 3.22, m, 4H; 3.80, quart., 2H; 4.21, t, 2H, 7.15, d, 2H, 7.95, dd, 1H, 8.55, d, 1H; 9.75, s, 1H.

EXAMPLE 64 N-[2-(3,4-Dimethoxy-phenyl)ethyl]-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 59 mg (0.3 mmol) of N-methyl-3,4-dimethoxyphenylethylamine, 45 mg (78%) of N-[2-(3,4-dimethoxyphenyl)-ethyl]-N-methyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.35 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 0.90, t, 3H; 1.07, t, 3H; 1.78, m, 2H; 1.92, m, 2H; 2.55, s, 3H; 2.73, s, 3H; 2.78, m, 2H; 2.89, t, 2H; 3.23, t, 2H, 3.80, s, 6H, 4.15, t, 2H, 6.65, m, 3H, 7.05, d, 1H, 7.75, dd, 1H, 8.41, d, 1H, 9.67, s, 1H.

EXAMPLE 65 N-Allyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 31 mg (0.3 mmol) of allylhydroxyethylamine, 34 mg (70%) of N-allyl-N-(2-hydroxyethyl)-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.52 (dichloromethane/methanol=9:1)

200 MHz ¹H-NMR (CDCl₃):1.01, t, 3H; 1.15, t, 3H; 1.85, m, 2H; 1.99, m, 2H; 2.38, s, broad, 1H, 2.63, s, 3H; 3.00, t, 2H, 3.32, t, 2H, 3.86, t, 2H, 3.90, d, 2H; 4.25, t, 2H, 5.21, m, 2H, 5.71, m, 1H; 7.15, d, 1 h, 7.95, dd, 1H; 8.55, d, 1H, 9.77, s, 1H.

EXAMPLE 66 N-Allyl-N-cyclopentyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 38 mg (0.3 mmol) of allylcyclopentylamine, 33 mg (64%) of N-allyl-N-cyclopentyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.43 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃):1.01, t, 3H;1.15, t, 3H; 1.53, m, 9H; 2.00, m, 4H, 2.63, s, 3H; 3.00, t, 2H; 3.80, m, 2H, 4.21, t, 2H, 5.20, m, 2H; 5.88, m, 1H, 7.12, d, 1H, 7.95, dd, 1H, 8.55, d, 1H, 9.75, s, 1H.

EXAMPLE 67 N-Allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]-triazin-2-yl)-4-propoxybenzenesulphonamide

By the same method, starting with 42 mg (0.1 mmol) of 4-propoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 26 mg (0.3 mmol) of allylethylamine, 30 mg (64%) of N-allyl-N-ethyl-3-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-4-propoxy-benzenesulphonamide are obtained.

R_(f)=0.44 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃):1.01, t, 3H;1.15, t, 6H;1.89, m, 2H, 2.01, m, 2H, 2.63, s, 3H, 3.00, t, 2H, 3.27, quart., 2H, 3.87, d, 2H, 4.23, t, 2H, 5.20, m, 2H, 5.72, m, 1H; 7.15, d, 1H, 7.95, dd, 1H, 8.55, d, 1H; 9.80, s, 1H.

EXAMPLE 68 2-[2-Ethoxy-4-methoxy-5-(4-methylpiperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo-[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 0.5 ml of dichloromethane and admixed with a spatula tip of dimethylaminopyridine and 14 mg (0.136 mmol) of N-methylpiperazine, and the reaction mixture is stirred at room temperature overnight. Purification over silica gel gives 12.8 mg (55%) of 2-[2-ethoxy-4-methoxy-5-(4-methylpiperazine-1-sulphonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one.

R_(f)=0.22 (dichloromethane/methanol=20:1).

200 MHz ¹H-NMR (CDCl₃): 0.94, t, 3H; 1.55, t, 3H; 1.80, m, 2H; 2.24, s, 3H; 2.42, t, 4H; 2.55, s, 3H; 2.92, t, 2H; 3.19, t, 4H, 3.91, s, 3H; 4.25, quart., 2H; 6.48, s, 1H; 8.57, s, 1H; 9.54, s, 1H.

EXAMPLE 69 2-{2-Ethoxy-5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-4-methoxy-phenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 18 mg (0.14 mmol) of 4-hydroxyethylpiperazine, 11 mg (46%) of 2-{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-4-methoxyphenyl}-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.34 (dichloromethane/methanol=15:1)

200 MHz ¹H-NMR (CDCl₃): 0.94, t, 3H; 1.55, t, 3H; 1.80, m, 3H; 2.52, m, 9H; 2.92, t, 2H; 3.20, t, 4H; 3.44, t, 2H; 3.92, s, 3H; 4.25, quart., 2H; 6.49, s, 1H; 8.56, s, 1H; 9.55, s, 1H.

EXAMPLE 70 4-Ethoxy-N-ethyl-N-(2-hydroxyethyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide

By the same method, starting from 20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 12 mg (0.14 mmol) of ethylhydroxyethylamine, 8 mg (34%) of 4-ethoxy-N-ethyl-N-(2-hydroxyethyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.

R_(f)=0.45 (dichloromethane/methanol=15:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.18, t, 3H; 1.61, t, 2H; 1.88, m, 2H; 2.39, s, broad, 1H; 2.65, s, 3H; 3.00, t, 2H; 3.38, quart., 2H; 3.45, t, 2H; 3.78, m, 2H; 4.01, s, 3H; 4.20, quart., 2H; 6.58, s, 1H; 8.67, s, 1H; 9.61, s, 1H.

EXAMPLE 71 4-Ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide

By the same method, starting with 20 mg (0.045 mmol) of 4-ethoxy-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzene-sulphonyl chloride and 19 mg (0.14 mmol) of 4-ethoxyaniline, 7 mg (34%) of 4-ethoxy-N-(4-ethoxyphenyl)-2-methoxy-5-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonamide are obtained.

R_(f)=0.36 (dichloromethane/methanol=20:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.33, t, 3H, 1.59, t, 3H, 1.86, hex., 2H, 2.62, s, 3H; 3.02, t, 2H; 3.92, quart., 2H; 4.11, s, 3H; 4.31, quart., 2H; 6.58, s, 1H, 6.72, d, 2H; 6.88, s, broad, 1H; 6.99, d, 2H, 8.50, s, 1H; 9.59, s, 1H.

EXAMPLE 72 4-Ethoxy-N-ethyl-N-(2-hydroxy-ethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)benzenesulphonamide

0.64 g (1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride are dissolved in 20 ml of dichloromethane and cooled to 0° C. After addition of a spatula tip of dimethylaminopyridine, 0.40 g (4.50 mmol) of 2-(ethylamino)-ethanol are added, and the reaction mixture is stirred at room temperature overnight. The mixture is diluted with dichloromethane, the organic phase is washed with water and dried over sodium sulphate and the solvent is removed under reduced pressure. Chromatography (dichloromethane/methanol=95:5) gives 0.454 g (63%) of a colourless solid.

200 MHz ¹H-NMR (CDCl₃):1.02, t, 3H; 1.20, t, 3H; 1.35, t, 3H; 1.61, t, 3H; 1.88, sex., 2H; 2.25, s, broad, 1H; 3.01, m, 4H; 3.32, m, 4H; 3.70, m, 2H; 3.80, m, 2H; 4.37, quart., 2H; 7.15, d, 1H; 7.98, dd, 1H; 8.56, d, 1H; 9.70, s, 1H.

EXAMPLE 73 N-(2-Methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide

By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 21 mg (0.282 mmol) of 2-methoxyethylamine, 15 mg (34%) of N-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide are obtained.

R_(f)=0.2 (ethyl acetate/cyclohexane=2:1)

200 MHz ¹H-NMR (CDCl₃): 0.97, t, 3H;1.25, t, 3H; 1.53, t, 3H; 1.82, sex., 2H; 2.97, m, 4H; 3.11, m, 2H; 3.22, s, 3H; 3.39, t, 2H; 4.37, quart., 2H; 5.00, t, 1H; 7.17, d, 1H, 7.97, dd, 1H, 8.53, d, 1H; 9.82, s, 1H.

EXAMPLE 74 N,N-Bis-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide

By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 38 mg (0.28 mmol) of bismethoxyethylamine, 17 mg (34%) of N,N-bis-(2-methoxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxybenzenesulphonamide are obtained.

R_(f)=0.34 (ethyl acetate/cyclohexane=2:1)

200 MHz ¹H-NMR (CDCl₃): 0.97, t, 3H;1.27, t, 3H; 1.53, t, 3H; 1.80, sex., 2H; 2.95, m, 4H; 3.22, s, 6H; 3.39, m, 4H; 3.49, m, 4H; 4.27, quart., 2H; 7.17, d, 1H, 7.97, dd, 1H, 8.53, d, 1H; 9.82, s, 1H.

EXAMPLE 75 2-[5-(4-Hydroxypiperidine-1-sulphonyl)-2-ethoxyphenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

By the same method, starting with 640 mg (1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 460 mg (4.5 mmol) of 4-hydroxypiperidine, 485 mg (66%) of 2-[5-(4-hydroxy-piperidine-1-sulphonyl)-2-ethoxyphenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.37 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 1.02, t, 3H; 1.32, t, 3H; 1.60, t, 3H; 1.80, m, 7H; 2.97, m, 6H; 3.30, m, 2H; 3.82, m, 1H; 4.34, quart., 2H; 7.17, d, 1H; 7.90, dd, 1H, 8.45, d, 1H. 9.75, s, 1H.

EXAMPLE 76 2-[5-(4-Hydroxymethylpiperidine-1-sulphonyl)-2-ethoxy-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 33 mg (0.28 mmol) of 4-hydroxymethylpiperidine, 23 mg (48%) of 2-[5-(4-hydroxymethylpiperidine-1-sulphonyl)-2-ethoxyphenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.38 (dichloromethane/methanol=10:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.33, t, 3H; 1.60, t, 3H; 1.80, m, 8H; 2.41, m, 2H, 3.00, m, 4H; 3.56, m, 4H; 4.35, quart, 2H; 7.17, d, 1H; 7.88, dd, 1H, 8.45, d, 1H; 9.71, s, 1H.

EXAMPLE 77 2-{2-Ethoxy-5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-phenyl}-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

By the same method, starting with 40 mg (0.094 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 37 mg (0.28 mmol) of 4-hydroxyethylpiperazine, 35 mg (71%) of 2-{2-ethoxy-5-[4-(2-hydroxyethyl)-piperazine-1-sulphonyl]-phenyl}-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.65 (dichloromethane/methanol=10:1)

EXAMPLE 78 2-[2-Ethoxy-5-(4-methylpiperazine-1-sulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f]-[1,2,4]triazin-4-one

By the same method, starting with 640 mg (1.50 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 450 mg (4.5 mmol) of 4-hydroxyethylpiperazine, 495 mg (66%) of 2-[2-ethoxy-5-(4-methylpiperazine-1-sulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are obtained.

R_(f)=0.30 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃):1.01, t, 3H; 1.35, t, 3H; 1.61, t, 3H; 1.89, sex., 2H; 2.31, s, 3H; 2.53, m, 4H; 3.05, m, 8H; 4.35, quart., 2H; 7.17, d, 1H; 7.89, dd, 1H; 8.48, d, 1H; 9.65, s, 1H.

EXAMPLE 79 2-[2-Ethoxy-5-(4-methylpiperazine-1-sulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride

300 mg (0.61 mmol) of 2-[2-ethoxy-5-(4-methyl-piperazine-1-sulphonyl)-phenyl]-5-ethyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one are dissolved in a mixture of ether and dichloromethane and admixed with 2 ml of a 1M solution of HCl in ether. After 20 minutes, the precipitated solid is filtered off with suction and dried.

200 MHz ¹H-NMR (DMSO-d₆): 0.95, t, 3H; 1.32, 2t, 6H; 1.80, sex., 2H; 2.76, m, 4H; 3.01, m, 4H; 3.15, m, 2H; 3.44, m, 2H; 3.81, m, 2H; 4.25, quart., 2H; 7.49, d, 1H; 7.95, m, 2H; 11.25, s, 1H; 12.30, s, 1H.

EXAMPLE 80 3-(5-Ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-ethoxybenzenesulphonamide

By the same method, starting with 640 mg (1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 650 mg (4.5 mmol) of 1-(3-aminopropyl)-morpholine, 476 mg (59%) of 3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-N-(3-morpholin-4-yl-propyl)-4-ethoxy-benzenesulphonamide are obtained.

R_(f)=0.18 (dichloromethane/methanol=19:1)

200 MHz ¹H-NMR (CDCl₃): 1.01, t, 3H; 1.32, t, 3H; 1.60, t, 3H; 1.70, m, 3H; 1.89, sex., 2H; 2.43, m, 7H; 3.01, m, 4H; 3.15, t, 2H; 3.70, m, 4H; 4.35, quart., 2H; 7.15, d, 1H; 7.95, dd, 1H; 8.55, d, 1H; 9.82, s, 1H.

EXAMPLE 81 N-(2-Hydroxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-N-propyl-benzenesulphonamide

By the same method, starting with 640 mg (1.5 mmol) of 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydroimidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and 464 mg (4.5 mmol) of propylhydroxyethylamine, 600 mg (81%) of N-(2-hydroxyethyl)-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-4-ethoxy-N-propylbenzenesulphonamide are obtained.

R_(f)=0.73 (dichloromethane/methanol=10:1)

200 MHz ¹H-NMR (CDCl₃): 0.91, t, 3H; 1.01, t, 3H; 1.32, t, 3H; 1.62, m, 5H; 1.88, m, 2H; 2.32, s, 1H; 3.01, m, 4H; 3.22, m, 4H; 3.80, m, 2H; 4.35, t, 2H; 7.15, d, 2H, 7.95, dd, 1H, 8.55, d, 1H; 9.75, s, 1H.

The sulphonamides listed in Tables 1, 2, 3, 4 and 6 below were prepared by means of automated parallelsynthesis from 4-ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and the appropriate amine using one of the three standard procedures below.

The sulphonamides listed in Table 5 were prepared by the same methods by means of automated parallelsynthesis from 4-ethoxy-3-(5-ethyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-δ][1,2,4]triazin-2-yl)-benzenesulphonyl chloride and the appropriate amine.

The purity of the final products was determined by means of HPLC, and they were characterized by LC-MS. The content of the desired compound according to HPLC-MS is given in per cent in the tables in the column “HPLC”. Standard procedure A was used with amines having acidic functionalities, standard procedure B was used with amines having neutral functionalities, standard procedure C was used with amines having additional basic functionalities.

In the structural formulae of Tables 1, 2, 3, 4, 5 and 6 below, hydrogen atoms are in some cases not shown. Nitrogen atoms having a free valency are therefore to be understood as —NH— radical.

Standard procedure A: Reaction of amines having acidic functionalities 0.05 mmol of amine, 0.042 mmol of sulphonyl chloride and 0.10 mmol of Na₂CO₃ are initially charged, and 0.5 ml of a mixture of THF/H₂O is pipetted in by hand. After 24 h at RT, the mixture is admixed with 0.5 ml of 1M H₂SO₄ solution and filtered through a two-phase cartridge (500 mg of Extrelut (upper phase) and 500 mg of SiO₂, mobile phase ethyl acetate). The product is obtained after concentrating the filtrate under reduced pressure.

Standard procedure B: Reaction of amines having neutral functionalities 0.125 mmol of amine are initially charged and 0.03 mmol of sulphonyl chloride as a solution in 1,2-dichloroethane is pipetted in by the synthesizer. After 24 h, the mixture is admixed with 0.5 ml of 1M H₂SO₄ and filtered through a two-phase cartridge (500 mg of Extrelut (upper phase) and 500 mg of SiO₂, mobile phase: ethyl acetate). The filtrate is concentrated under reduced pressure.

Standard procedure C: Reaction of amines having basic functionalities 0.05 mmol of amine are initially charged and 0.038 mmol of sulphonyl chloride as a solution in 1,2-dichloroethane and 0.05 mmol of triethylamine as a solution in 1,2-dichloroethane is pipetted in by the synthesizer. After 24 h, the solution is initially admixed with 3 ml of saturated NaHCO₃ solution and the reaction mixture is filtered through a two-phase cartridge. The product is obtained after concentrating the filtrate under reduced pressure.

All reactions are monitored by thin-layer chromatography. If the reaction is not complete after 24 h at RT, the mixture is heated to 60° C. for a further 12 h and the experiment is subsequently terminated. TABLE 1 MW Ex. No. Structure [g/mol] HPLC MZ + H 82

525.6315 83 526 83

525.6315 71 526 84

555.658 91 556 85

477.5869 76 478 86

525.6315 81 526 87

463.5598 65 464 88

531.6793 83 532 89

463.5598 40 464 90

463.5598 44 464 91

581.6962 76 582 92

475.5273 61 476 93

421.4785 80 422 94

475.5709 81 476 95

491.614 97 492 96

567.7127 80 568 97

521.6405 94 522 98

477.5869 70 478 99

535.6239 88 536 100

553.6857 88 554 101

529.6197 85 530 102

539.6586 91 540 103

520.6121 55 521 104

502.6404 82 503 105

564.7121 86 565 106

524.6467 85 525 107

538.6738 85 539 108

546.694 84 547 109

504.6127 90 505

TABLE 2 MW Ex. No. Structure [g/mol] HPLC MZ + H 110

507.61336 74 508 111

539.65856 75 540 112

599.71154 83 600 113

535.66754 60 536 114

521.64045 95 522 115

569.68505 84 570 116

608.54862 85 608 117

569.68505 88 570 118

463.55978 94 464 119

535.66754 93 536 120

517.6522 71 518 121

561.70578 92 562 122

539.65856 85 540 123

518.68341 87 519 124

588.13068 30 588 125

550.68498 83 551 126

542.70571 77 543 127

502.64038 91 503 128

490.62923 45 491 129

568.70032 66 569 130

534.68281 86 535 131

580.7551 95 581 132

576.72045 87 577 133

598.72958 60 599 134

516.66747 95 517 135

528.67862 80 529 136

538.67383 85 539 137

533.69808 68 534 138

516.66747 91 517 139

489.59802 85 490 140

475.57093 83 476 141

503.62511 85 504 142

489.59802 91 490 143

461.54384 78 462 144

539.65856 88 540 145

539.65856 58 538 146

511.60438 80 512 147

505.64105 90 506

TABLE 3 MW Ex. No. Structure [g/mol] HPLC MZ + H 148

565.70 38 566 149

643.77 85 644 150

525.63 80 526 151

525.63 78 526 152

560.63 51 561 153

503.65 78 504 154

522.63 82 523 155

502.60 84 503 156

488.57 83 489 157

536.66 82 537 158

490.63 90 491 159

537.65 83 538 160

504.66 91 505 161

589.81 65 590 162

488.61 88 489 163

566.73 32 567 164

501.61 75 502 165

491.61 91 492 166

477.59 73 478 167

525.63 81 526 168

488.57 70 489 169

511.60 76 512 170

568.70 50 569 171

554.67 63 555 172

582.73 50 583 173

637.76 30 638 174

554.67 70 555 175

568.70 44 569

TABLE 4 MW Ex. No. Structure [g/mol] HPLC MZ + H 176

477.59 82 478 177

491.61 89 492 178

505.64 88 506 179

513.62 47 514 180

504.66 83 505 181

552.70 83 553 182

492.60 72 493 183

593.75 52 594 184

504.66 82 505 185

582.75 59 583 186

566.68 60 567 187

579.73 30 580 188

548.63 73 549 189

548.63 72 549 190

559.67 54 560 191

511.60 70 512 192

580.76 68 581 193

476.60 89 477 194

583.71 80 584 195

505.64 84 506 196

518.68 40 519 197

528.68   82 ? 529 198

566.68 63 567 199

553.69 87 554 200

491.61 84 492

TABLE 5 Ex. No. Structure MW HPLC MZ + H 201

516.67 87 517 202

502.64 84 503 203

516.67 87 517 204

538.67 91 539 205

533.7 85 534 206

518.68 77 519 207

566.73 92 567 208

552.7 87 553 209

506.63 52 507 210

560.72 62 561 211

568.7 88 569 212

582.73 89 583 213

580.71 83 581 214

518.64 89 519 215

463.56 90 464 216

548.71 78 549 217

490.63 87 491 218

532.71 93 533 219

564.71 91 565 220

556.73 92 557 221

516.67 92 517 222

504.66 83 505 223

558.75 90 559 224

532.71 86 533 225

572.78 68 573 226

582.73 87 583 227

548.71 85 549 228

594.78 97 595 229

590.75 90 591 230

530.69 95 531 231

542.71 88 543 232

552.7 91 553 233

534.68 65 535 234

520.66 83 521 235

530.69 89 531 236

542.71 70 543 237

580.71 81 581 238

504.66 81 505 239

551.67 86 552 240

518.68 85 519 241

502.64 85 503 242

580.76 79 581

TABLE 6 Ex. No. Structure MW HPLC MZ + H 243

477.5869 86 478 244

495.605 62 496 245

511.6044 50 512 246

564.495 40 565 247

555.658 61 556 248

497.5773 60 498 249

581.6963 77 582 250

557.6303 76 558 251

539.615 74 540 252

515.5677 64 516 253

472.5266 38 473 254

459.5715 88 460 255

551.5486 78 552 256

574.6824 59 575 257

497.5773 40 498 258

459.5715 90 460 259

473.5986 80 474 260

461.5439 83 462 261

503.6687 71 504 262

517.6086 71 518 263

511.6044 76 512 264

518.5989 74 519 265

552.6573 91 553 266

566.6844 71 567 267

567.6692 48 568 268

477.6084 90 478 269

569.6851 73 570 270

651.766 65 652 271

541.6309 71 542 272

607.6133 39 608 273

511.6044 92 512 274

589.7164 >95 590 275

477.5869 >95 478 276

463.5598 64 464 277

449.5327 >95 450 278

507.6134 >95 508 279

532.6232 >95 533 280

560.6775 89 561 281

636.8199 88 637 282

476.5585 50 477 283

489.5981 93 490 284

622.7928 68 623 285

608.7657 >95 609 286

583.6873 85 584 287

511.6044 >95 512 288

541.6309 >95 542 289

541.6309 >95 542 290

571.6574 73 572 291

569.6851 83 570 292

597.7393 89 598 293

581.6963 76 582 294

609.7504 83 610 295

609.7504 77 610 296

583.7122 82 584 297

611.7227 88 612 298

571.6574 89 572 299

567.6692 81 568 300

627.7221 82 628 301

661.7396 64 662 302

599.668 77 600 303

555.658 83 556 304

654.7916 60 655 305

626.7374 86 627 306

627.7221 82 628 307

583.7122 81 584 308

631.7568 29 632 309

569.6851 60 570 310

597.7393 62 598 311

581.6963 87 582 312

609.7504 71 610 313

633.7291 47 634 314

570.629 59 571 315

633.7291 35 634 316

583.7122 51 584 317

611.7227 51 612 318

571.6574 75 572 319

603.7026 64 604 320

567.6692 74 568 321

597.652 88 598 322

627.7221 80 628 323

647.7562 47 648 324

555.658 43 556 325

654.7916 54 655 326

624.7214 71 625 327

689.8375 42 690 328

583.7122 40 584 329

555.658 49 556 330

525.6315 83 526 331

525.6315 71 526 332

555.658 91 556 333

477.5869 76 478 334

478.5745 62 479 335

490.6292 42 491

EXAMPLE 336 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazol[5,1-f][1,2,4]triazine-4-one hydrochloride trihydrate

If the free base from Example 19 is crystallized from a mixture of an organic solvent and dilute aqueous hydrochloric acid, a hydrochloride trihydrate is obtained.

m.p.: 218° C.

Water content: 9.4% (K. Fischer)

Chloride content: 6.1%

EXAMPLE 337 2-[2-Ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazine-4-one dihydrochloride

0.35 g (0.712 mmol) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazine-4-one are suspended in 8 ml of ether and dichloromethane is added until a homogeneous solution is formed. 24 ml of a 1M solution of HCl in ether are added and the mixture is stirred at room temperature for 20 minutes and filtered off with suction. This gives 372 mg (99%) of 2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulphonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazine-4-one dihydrochloride.

200 MHz ¹H-NMR (DMSO-d₆): 0.96, t, 3H; 1.22, t, 3H; 1.36, t, 3H; 1.82, sex., 2H; 2.61, s, 3H; 2.88, m, 2H; 3.08, m, 6H; 3.50, m, 2H; 3.70, m, 2H; 4.25, quart., 2H; 7.48, d, 1H; 7.95, m, 2H; 11.42, s, 1H; 12.45, s, 1H. 

1. 2-Phenyl-substituted imidazotriazinones of the general formula (I)

in which R¹ represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, R² represents straight-chain alkyl having up to 4 carbon atoms, R³ and R⁴ are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 8 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 10 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of trifluoromethyl, trifluoromethoxy, hydroxyl, halogen, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 6 carbon atoms and/or by radicals of the formulae —SO₃H, -(A)_(a)-NR⁷R⁸, —O—CO—NR⁷′R⁸′, —S(O)_(b)—R⁹, —P(O)(OR¹⁰)(OR¹¹),

in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO₂, R⁷, R⁷′, R⁸ and R⁸′ are identical or different and each represents hydrogen, or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms, a 5- to 6-membered unsaturated, partially unsaturated or saturated, optionally benzo-fused heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, halogen, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula —(SO₂)_(c)—NR¹²R¹³, in which c represents a number 0 or 1, R¹² and R¹³ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or R⁷, R⁷′, R⁸ and R⁸′ each represent straight-chain or branched alkoxy having up to 6 carbon atoms, or represents straight-chain or branched alkyl having up to 8 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, aryl having 6 to 10 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms or by a group of the formula —(CO)_(d)—NR¹⁴R¹⁵, in which R¹⁴ and R¹⁵ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and d represents a number 0 or 1, or R⁷ and R⁸ and/or R⁷′ and R⁸′ together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O or a radical of the formula —NR¹⁶, in which R¹⁶ represents hydrogen, aryl having 6 to 10 carbon atoms, benzyl, a 5- to 7-membered aromatic or saturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O which is optionally substituted by methyl, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, R⁹ represents aryl having 6 to 10 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms, R¹⁰ and R¹¹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or the alkyl chain listed above under R³/R⁴ is optionally substituted by cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or by a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N and O or a radical of the formula —NR¹⁷, in which R¹⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 6 carbon atoms, and where aryl and the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of nitro, halogen, —SO₃H, straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy and/or by a radical of the formula —SO₂—NR¹⁸R¹⁹, in which R¹⁸ and R¹⁹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, and/or R³ or R⁴ represents a group of the formula —NR²⁰R²¹, in which R²⁰ and R²¹ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, and/or R³ or R⁴ represents adamantyl, or represents radicals of the formulae

or represents cycloalkyl having 3 to 8 carbon atoms, aryl having 6 to 10 carbon atoms or represents a 5- to 7-membered partially unsaturated, saturated or unsaturated, optionally benzo-fused heterocycle which may contain up to 4 heteroatoms from the group consisting of S, N and O, or a radical of the formula —NR²², in which R²² has the meaning of R¹⁶ given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 5 carbon atoms, and where cycloalkyl, aryl and/or the heterocycle are optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and/or by groups of the formulae —SO₃H, —OR²³, (SO₂)_(e)NR²⁴R²⁵, —P(O)(OR²⁶)(OR²⁷), in which e represents a number 0 or 1, R²³ represents a radical of the formula

represents cycloalkyl having 3 to 7 carbon atoms, or represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by cycloalkyl having 3 to 7 carbon atoms, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, carboxyl, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl and halogen, and/or alkyl which is optionally substituted by radicals of the formulae —CO—NR R²⁹ or —CO—R³⁰, in which R²⁸ and R²⁹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 8 carbon atoms, or R²⁸ and R²⁹ together with the nitrogen atom form a 5- to 7-membered saturated heterocycle which may optionally contain a further heteroatom from the group consisting of S and O, and R³⁰ represents phenyl or adamantyl, R²⁴ and R²⁵ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, R²⁶ and R²⁷ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them and/or cycloalkyl, aryl and/or the heterocycle are optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl, carboxyl, by a 5- to 7-membered heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, or by groups of the formula —SO₂—R³¹, P(O)(OR³²)(OR³³) or —NR³⁴R³⁵, in which R³¹ represents hydrogen or has the meaning of R⁹ given above and is identical to or different from it, R³² and R³³ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them, R³⁴ and R³⁵ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms which is optionally substituted by hydroxyl or by straight-chain or branched alkoxy having up to 4 carbon atoms, or R³⁴ and R³⁵ together with the nitrogen atom form a 5- to 6-membered saturated heterocycle which may contain a further heteroatom from the group consisting of S and O, or a radical of the formula —NR³⁶, in which R³⁶ represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 7 carbon atoms or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, or R³ and R⁴ together with the nitrogen atom form a 5- to 7-membered unsaturated or saturated or partially unsaturated, optionally benzo-fused heterocycle which may optionally contain up to 3 heteroatoms from the group consisting of S, N and O, or a radical of the formula —NR³⁷, in which R³⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by groups of the formula -(D)_(f)-NR³⁸R³⁹, —CO—(CH₂)_(g)—O—CO—R⁴⁰, —CO—(CH₂)_(h)—OR⁴¹ or —P(O)(OR⁴²)(OR⁴³), in which g and h are identical or different and each represents a number 1, 2, 3 or 4, and f represents a number 0 or 1, D represents a group of the formula —CO or —SO₂, R³⁸ and R³⁹ are identical or different and each has the meaning of R⁷ and R⁸ given above, R⁴⁰ represents straight-chain or branched alkyl having up to 6 carbon atoms, R⁴¹ represents straight-chain or branched alkyl having up to 6 carbon atoms, R⁴² and R⁴³ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R³⁷ represents a radical of the formula —(CO)_(i)-E, in which i represents a number 0 or 1, E represents cycloalkyl having 3 to 7 carbon atoms or benzyl, represents aryl having 6 to 10 carbon atoms or a 5- to 6-membered aromatic heterocycle having up to 4 heteroatoms from the group consisting of S, N and O, where the abovementioned ring systems are optionally mono- or polysubstituted by identical or different constituents selected from the group consisting of nitro, halogen, —SO₃H, straight-chain or branched alkoxy having up to 6 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy, or by a radical of the formula —SO₂—NR⁴⁴R⁴⁵, in which R⁴⁴ and R⁴⁵ have the meaning of R¹⁸ and R¹⁹ given above and are identical to or different from them, or E represents radicals of the formulae

and the heterocycle listed under R³ and R⁴, which is formed together with the nitrogen atom, is optionally mono- or polysubstituted, if appropriate also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 6 carbon atoms, nitro and groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷),

in which R⁴⁶ and R⁴⁷ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them, R⁴⁸ represents hydroxyl or straight-chain or branched alkoxy having up to 4 carbon atoms, represents a number 0 or 1, and R⁴⁹ and R⁵⁰ are identical or different and have the meanings of R¹⁴ and R¹⁵ given above, and/or the heterocycle listed under R³ and R⁴, which is formed together with the nitrogen atom, is optionally substituted by straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, halogen, carboxyl, cycloalkyl or cycloalkyloxy having in each case 3 to 8 carbon atoms, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 6 carbon atoms, or by a radical of the formula —SO₃H, —NR⁵¹R⁵² or P(O)OR⁵³OR⁵⁴, in which R⁵¹ and R⁵² are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, R⁵³ and R⁵⁴ are identical or different and have the meanings of R¹⁰ and R¹¹ given above, and/or the alkyl is optionally substituted by aryl having 6 to 10 carbon atoms which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, hydroxyl, straight-chain or branched alkoxy having up to 6 carbon atoms, or by a group of the formula —NR⁵¹′R⁵²′, in which R⁵¹′ and R⁵²′ have the meanings of R⁵¹ and R52 given above and are identical to or different from them, and/or the heterocycle listed under R³ and R⁴, which is formed together with the nitrogen atom, is optionally substituted by aryl having 6 to 10 carbon atoms or by a 5- to 7-membered saturated, partially unsaturated or unsaturated heterocycle having up to 3 heteroatoms from the group consisting of S, N and O, optionally also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 6 carbon atoms, or R³ and R⁴ together with the nitrogen atom form radicals of the formulae

R⁵ and R⁶ are identical or different and each represents hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms, hydroxyl or represents straight-chain or branched alkoxy having up to 6 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.
 2. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to claim 1 in which R¹ represents straight-chain or branched alkyl having up to 3 carbon atoms, R² represents straight-chain alkyl having up to 3 carbon atoms, R³ and R⁴ are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 6 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 8 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, benzyloxycarbonyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms, and by radicals of the formulae —SO₃H, -(A)_(a)-NR⁷R⁸, —O—CO—NR⁷′R⁸′, —S(O)_(b)—R⁹, —P(O)(OR¹⁰)(OR¹¹),

in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO₂, R⁷, R⁷′, R⁸ and R⁸′ are identical or different and each represents hydrogen, or cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula —(SO₂)_(c)—NR¹²R¹³, in which c represents a number 0 or 1, R¹² and R¹³ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R⁷, R⁷′, R⁸ and R⁸′ each represent straight-chain or branched alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 7 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a group of the formula —(CO)_(d)—NR¹⁴R¹⁵, in which R¹⁴ and R¹⁵ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and d represents a number 0 or 1, or R⁷ and R⁸ and/or R⁷′ and R⁸′ together with the nitrogen atom form a pyrrolidinyl, morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae

in which R¹⁶ represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl, R⁹ represents straight-chain or branched alkyl having up to 3 carbon atoms, R¹⁰ and R¹¹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or the alkyl chain listed under R³/R⁴ is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, pyridyl, quinolyl, pyrrolidinyl, pyrimidyl, morpholinyl, furyl, piperidinyl, tetrahydrofuranyl or by radicals of the formulae

in which R¹⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl or alkoxy having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl and straight-chain or branched alkoxy having up to 4 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, —SO₃H, straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, hydroxyl, and/or by a radical of the formula —SO₂—NR¹⁸R¹⁹, in which R¹⁸ and R¹⁹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, and/or R³ or R⁴ represents a group of the formula —NR²⁰R²¹, in which R²⁰ and R²¹ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, and/or R³ or R⁴ represents adamantyl, or represents radicals of the formulae

or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl or represents radicals of the formulae

in which R²² has the meaning of R¹⁶ given above and is identical to or different from it, or represents carboxyl, formyl or straight-chain or branched acyl having up to 3 carbon atoms, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, trifluoromethyl, trifluoromethoxy, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and/or by groups of the formulae —S_(O) ₃H, —OR²³, (SO₂)_(e)NR²⁴R²⁵, —P(O)(OR²⁶)(OR²⁷), in which e represents a number 0 or 1, R²³ represents a radical of the formula

represents cyclopropyl, cyclopentyl, cyclobutyl, cyclohexyl or cycloheptyl, represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms which may optionally be substituted by cyclopropyl, cyclopentyl, cyclohexyl, benzyloxy, tetrahydropyranyl, tetrahydrofuranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or polysubstituted by identical or different substituents selected from the group consisting of straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, fluorine and chlorine, and/or where alkyl is optionally substituted by radicals of the formulae —CO—NR²⁸R²⁹ or —CO—R³⁰, in which R²⁸ and R²⁹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms, or R²⁸ and R²⁹ together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and R³⁰ represents phenyl or adamantyl, R²⁴ and R²⁵ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, R²⁶ and R²⁷ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, triazolyl or by groups of the formula —SO₂—R³¹, —P(O)(OR³²)(OR³³) or —NR³⁴R³⁵, in which R³¹ has the meaning of R⁹ given above and is identical to or different from it, R³² and R³³ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them, R³⁴ and R³⁵ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 5 carbon atoms which is optionally substituted by hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, or R³⁴ and R³⁵ together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula

in which R³⁶ represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 5 carbon atoms or straight-chain or branched alkyl having up to 4 carbon atoms which is optionally substituted by hydroxyl, or R³ and R⁴ together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula

in which R³⁷ represents hydrogen, hydroxyl, formyl, trifluoromethyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or represents straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, trifluoromethyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by groups of the formula -(D)NR³⁸R³⁹, —CO—(CH₂)_(g)—O—CO—R⁴⁰, —CO—(CH₂)_(h)—OR⁴¹ or —P(O)(OR⁴²)(OR⁴³), in which g and h are identical or different and each represents a number 1, 2 or 3, and f represents a number 0 or 1, D represents a group of the formula —CO or —SO₂, R³⁸ and R³⁹ are identical or different and have the meanings of R⁷ and R⁸ given above, R⁴⁰ represents straight-chain or branched alkyl having up to 4 carbon atoms, R⁴¹ represents straight-chain or branched alkyl having up to 4 carbon atoms, R⁴² and R⁴³ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R³⁷ represents a radical of the formula —(CO)_(i)-E, in which i represents a number 0 or 1, E represents cyclopentyl, cyclohexyl, cycloheptyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, —SO₃H, straight-chain or branched alkoxy having up to 4 carbon atoms, hydroxyl, trifluoromethyl, trifluoromethoxy or by a radical of the formula —SO₂—NR⁴⁴R⁴⁵, in which R⁴⁴ and R⁴⁵ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, or E represents radicals of the formulae

and the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 5 carbon atoms, nitro and groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷),

in which R⁴⁶ and R⁴⁷ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them, R⁴⁸ represents hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, j represents a number 0 or 1, and R⁴⁹ and R⁵⁰ are identical or different and have the meanings of R¹⁴ and R¹⁵ given above, and/or the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 5 carbon atoms which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 4 carbon atoms, or by a radical of the formula —SO₃H, —NR⁵¹R⁵² or —P(O)OR⁵³OR⁵⁴, in which R⁵¹ and R⁵² are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 4 carbon atoms, R⁵³ and R⁵⁴ are identical or different and have the meanings of R¹⁰ and R¹¹ given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, straight-chain or branched alkoxy having up to 4 carbon atoms, or by a group of the formula —NR⁵¹′R⁵²′, in which R⁵¹′ and R⁵²′ have the meanings of R⁵¹ and R⁵² given above and are identical to or different from them, and/or the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, optionally also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 5 carbon atoms, or R³ and R⁴ together with the nitrogen atom form radicals of the formulae

R⁵ and R⁶ are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 4 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.
 3. 2-Phenyl-substituted imidazotriazinones of the general formula (I) according to claim 1 in which R¹ represents straight-chain or branched alkyl having up to 3 carbon atoms, R² represents straight-chain alkyl having up to 3 carbon atoms, R³ and R⁴ are identical or different and each represents hydrogen or represents straight-chain or branched alkenyl or alkoxy having in each case up to 4 carbon atoms, or represents a straight-chain or branched alkyl chain having up to 6 carbon atoms which is optionally interrupted by an oxygen atom and which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, straight-chain or branched alkoxycarbonyl having up to 4 carbon atoms, and/or by radicals of the formulae —SO₃H, -(A)_(a)-NR⁷R⁸, —O—CO—NR⁷′R⁸′, —S(O)_(b)—R⁹, —P(O)(OR¹⁰)(OR¹¹),

in which a and b are identical or different and each represents a number 0 or 1, A represents a radical CO or SO₂, R⁷, R⁷′, R⁸ and R⁸′ are identical or different and each represents hydrogen, or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, piperidinyl and pyridyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, nitro, carboxyl, fluorine, chlorine, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula —(SO₂)_(c)NR¹²R¹³, in which c represents a number 0 or 1, R¹² and R¹³ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or R⁷, R⁷′, R⁸ and R⁸′ each represent methoxy, or represent straight-chain or branched alkyl having up to 6 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, phenyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a group of the formula —(CO)_(d)—NR¹⁴R¹⁵, in which R¹⁴ and R¹⁵ are identical or different and each represents hydrogen, methyl or ethyl, and d represents a number 0 or 1, or R⁷ and R⁸ and/or R⁷′ and R⁸′ together with the nitrogen atom form a morpholinyl, piperidinyl or triazolyl ring or radicals of the formulae

in which R¹⁶ represents hydrogen, phenyl, benzyl, morpholinyl, pyrrolidinyl, piperidinyl, piperazinyl or N-methylpiperazinyl, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, R⁹ represents methyl, R¹⁰ and R¹¹ are identical or different and each represents hydrogen, methyl or ethyl, and/or the alkyl chain listed under R³/R⁴ is optionally substituted by cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, morpholinyl, furyl, tetrahydrofuranyl, or by radicals of the formulae

in which R¹⁷ represents hydrogen, hydroxyl, formyl, acetyl or alkoxy having up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl or straight-chain or branched alkoxy having up to 3 carbon atoms, and where phenyl and the heterocycles are optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, —SO₃H, straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, hydroxyl, and/or by a radical of the formula —SO₂NR¹⁸R¹⁹, in which R¹⁸ and R¹⁹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, and/or R³ or R⁴ represents a group of the formula —NR²⁰R²¹, in which R²⁰ and R²¹ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, and/or R³ or R⁴ represents adamantyl, or represents radicals of the formulae

or represents cyclopentyl, cyclohexyl, cycloheptyl, phenyl, morpholinyl, oxazolyl, thiazolyl, quinolyl, isoxazolyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl, or represents radicals of the formulae

in which R²² has the meaning of R¹⁶ given above and is identical to or different from it, or represents formyl or acetyl, and where cycloalkyl, phenyl and/or the heterocycles are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, triazolyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 4 carbon atoms, nitro, and/or by groups of the formulae —SO₃H, —OR²³, (SO₂)_(e)NR²⁴R²⁵, —P(O)(OR²⁶)(OR²⁷), in which e represents a number 0 or 1, R²³ represents a radical of the formula

represents cyclopropyl, cyclopentyl, cyclobutyl or cyclohexyl, represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by cyclopropyl, cyclohexyl, benzyloxy, tetrahydropyranyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, benzyloxycarbonyl or phenyl which for its part may be mono- or disubstituted by identical or different substituents selected from the group consisting of methoxy, hydroxyl, fluorine or chlorine, and/or where alkyl is optionally substituted by radicals of the formulae —CO—NR²⁸R²⁹ or —CO—R³⁰, in which R²⁸ and R²⁹ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or R²⁸ and R²⁹ together with the nitrogen atom form a morpholinyl, pyrrolidinyl or piperidinyl ring, and R³⁰ represents phenyl or adamantyl, R²⁴ and R²⁵ have the meaning of R¹⁸ and R¹⁹ given above and are identical to or different from them, R²⁶ and R²⁷ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them and/or cycloalkyl, phenyl and/or the heterocycles are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms, which is optionally substituted by hydroxyl, carboxyl, pyridyl, pyrimidyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, triazolyl or by groups of the formula —SO₂—R³¹, P(O)(OR³²)(OR³³) or —NR³⁴R³⁵, in which R³¹ represents methyl, R³² and R³³ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them, R³⁴ and R³⁵ are identical or different and each represents hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl or methoxy, or R³⁴ and R³⁵ together with the nitrogen atom form a morpholinyl, triazolyl or thiomorpholinyl ring or a radical of the formula

in which R³⁶ represents hydrogen, hydroxyl, straight-chain or branched alkoxycarbonyl having up to 3 carbon atoms or straight-chain or branched alkyl having up to 3 carbon atoms which is optionally substituted by hydroxyl, or R³ and R⁴ together with the nitrogen atom form a morpholinyl, thiomorpholinyl, pyrrolidinyl, piperidinyl ring, or a radical of the formula

in which R³⁷ represents hydrogen, hydroxyl, formyl, straight-chain or branched acyl, alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formula -(D)_(f)-NR³⁸R³⁹, —CO—(CH₂)_(g)—O—CO—R⁴⁰, —CO—(CH₂)_(h)—OR⁴¹ or —P(O)(OR⁴²)(OR⁴³), in which g and h are identical or different and each represents a number 1 or 2, and f represents a number 0 or 1, D represents a group of the formula —CO or —SO₂, R³⁸ and R³⁹ are identical or different and have the meanings of R⁷ and R⁸ given above, R⁴⁰ represents straight-chain or branched alkyl having up to 3 carbon atoms, R⁴¹ represents straight-chain or branched alkyl having up to 3 carbon atoms, R⁴² and R⁴³ are identical or different and each represents hydrogen, methyl or ethyl, or R³⁷ represents a radical of the formula —(CO)_(i)-E, in which i represents a number 0 or 1, E represents cyclopentyl, benzyl, phenyl, pyridyl, pyrimidyl or furyl, where the abovementioned ring systems are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of nitro, fluorine, chlorine, —SO₃H, straight-chain or branched alkoxy having up to 3 carbon atoms, hydroxyl, or by a radical of the formula —SO₂—NR⁴⁴R⁴⁵, in which R⁴⁴ and R⁴⁵ have the meanings of R¹⁸ and R¹⁹ given above and are identical to or different from them, or E represents radicals of the formulae

and the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally mono- to trisubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷),

in which R⁴⁶ and R⁴⁷ have the meanings of R¹⁰ and R¹¹ given above and are identical to or different from them, R⁴⁸ represents hydroxyl or methoxy, j represents a number 0 or 1, and R⁴⁹ and R⁵⁰ are identical or different and have the meanings of R¹⁴ and R¹⁵ given above, and/or the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents selected from the group consisting of hydroxyl, fluorine, chlorine, carboxyl, cyclopropyl, cycloheptyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by a radical of the formula —SO₃H, —NR⁵¹R⁵² or P(O)OR⁵³OR⁵⁴, in which R⁵¹ and R⁵² are identical or different and each represents hydrogen, phenyl, carboxyl, benzyl or straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, R⁵³ and R⁵⁴ are identical or different and have the meanings of R¹⁰ and R¹¹ given above, and/or the alkyl is optionally substituted by phenyl which for its part may be mono- to disubstituted by identical or different substituents selected from the group consisting of fluorine, chlorine, hydroxyl, methoxy, or by a group of the formula —NR⁵¹R⁵², in which R⁵¹′ and R⁵²′ have the meanings of R⁵¹ and R⁵² given above and are identical to or different from them, and/or the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally substituted by phenyl, pyridyl, piperidinyl, pyrrolidinyl or tetrazolyl, if appropriate also attached via a nitrogen function, where the ring systems for their part may be substituted by hydroxyl or by straight-chain or branched alkyl or alkoxy having in each case up to 3 carbon atoms, or R³ and R⁴ together with the nitrogen atom form radicals of the formulae

R⁵ and R⁶ are identical or different and each represents hydrogen, hydroxyl or represents straight-chain or branched alkoxy having up to 3 carbon atoms, and their salts, hydrates, N-oxides and isomeric forms.
 4. 2-Phenyl-substituted imidazotriazinones of the general formula (1) according to claim 1 in which R¹ represents methyl or ethyl, R² represents ethyl or propyl, R³ and R⁴ are identical or different and each represents a straight-chain or branched alkyl chain having up to 5 carbon atoms which is optionally substituted up to two times by identical or different substituents selected from the group consisting of hydroxyl and methoxy, or R³ and R⁴ together with the nitrogen atom form a piperidinyl, morpholinyl, thiomorpholinyl ring, or a radical of the formula

in which R³⁷ represents hydrogen, formyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or represents straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, straight-chain or branched alkoxy or alkoxycarbonyl having in each case up to 3 carbon atoms, or by groups of the formulae -(D)_(f)-NR³⁸R³⁹ or —P(O)(OR⁴²)(OR⁴³), in which f represents a number 0 or 1, D represents a group of the formula —CO, R³⁸ and R³⁹ are identical or different and each represents hydrogen or methyl, R⁴² and R⁴³ are identical or different and each represents hydrogen, methyl or ethyl, or R³⁷ represents cyclopentyl, and the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally mono- or disubstituted, optionally also geminally, by identical or different substituents selected from the group consisting of hydroxyl, formyl, carboxyl, straight-chain or branched acyl or alkoxycarbonyl having in each case up to 3 carbon atoms, or groups of the formulae —P(O)(OR⁴⁶)(OR⁴⁷) or —(CO)_(i)NR⁴⁹R⁵⁰, in which R⁴⁶ and R⁴⁷ are identical or different and each represents hydrogen, methyl or ethyl, j represents a number 0 or 1, and R⁴⁹ and R⁵⁰ are identical or different and each represents hydrogen or methyl and/or the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally substituted by straight-chain or branched alkyl having up to 3 carbon atoms which is optionally mono- or disubstituted by identical or different substituents selected from the group consisting of hydroxyl, carboxyl, or by a radical of the formula P(O)OR⁵³OR⁵⁴, in which R⁵³ and R⁵⁴ are identical or different and each represents hydrogen, methyl or ethyl, and/or the heterocycles listed under R³ and R⁴, which are formed together with the nitrogen atom, are optionally substituted by pyrrolidinyl or piperidinyl attached via nitrogen, R⁵ represents hydrogen, and R⁶ represents ethoxy or propoxy, and their salts, hydrates, N-oxides and isomeric forms.
 5. 2-Phenyl-substituted imidazotriazinones according to claims 1 to 4 having the following structures: Structure


6. 2-Phenyl-substituted imidazotriazinones of the general formula (1) according to claim 1 for the treatment of disorders.
 7. Process for preparing 2-phenyl-substituted imidazotriazinones according to claim 1, characterized in that initially compounds of the general formula (II)

in which R¹ and R² are each as defined above and L represents straight-chain or branched alkyl having up to 4 carbon atoms, are converted with compounds of the general formula (III)

in which R⁵ and R⁶ are each as defined above, in a two-step reaction in the systems ethanol and phosphorus oxytrichloride/dichloroethane into the compounds of the general formula (IV)

in which R¹, R², R⁵ and R⁶ are each as defined above, which are reacted in a further step with chlorosulphonic acid to give the compounds of the general formula (V)

in which R¹, R², R⁵ and R⁶ are each as defined above, which are finally reacted with amines of the general formula (VI) HN³R⁴   (VI) in which R³ and R⁴ are each as defined above, in inert solvents.
 8. Pharmaceuticals which comprise at least one 2-phenyl-substituted imidazotriazinone according to claim 1 and pharmacologically acceptable formulating agents.
 9. Pharmaceuticals according to claim 8 for the treatment of cardiovascular, cerebrovascular disorders and/or disorders of the urogenital tract.
 10. Pharmaceuticals according to claim 9 for the treatment of erectile dysfunction.
 11. The use of 2-phenyl-substituted imidazotriazinones according to claim 1 for preparing pharmaceuticals. 